Biomedical subjects

Ning Liu

Publications and source records attributed to Ning Liu.

At least 19 recordsLinked to original sources

PubMed2026

Intramuscular patient-derived xenografts achieve high engraftment rates in gastric cancer: implications for pharmacodynamic testing and genomic biomarker discovery.

BACKGROUND: Gastric cancer (GC) exhibits marked inter-patient heterogeneity, limiting empirical chemotherapy efficacy. Patient-derived xenograft (PDX) models preserve the molecular features of parental tumors and can serve as pharmacodynamic surrogates, but conventional subcutaneous PDX suffers from low engraftment rates. This study evaluated an optimized intramuscular PDX platform for individualized drug testing in GC and applied whole exome sequencing (WES) for biomarker identification (Clinical trial registry: ChiCTR-OOC-17012731). MATERIALS AND METHODS: Ninety-eight treatment-naive GC patients were enrolled between April 2018 and December 2020. Fresh tumor tissues were engrafted into NCG mice by intramuscular transplantation. Drug efficacy was evaluated using tumor cell necrosis rate and Ki-67 expression. WES was performed on 32 engrafted tumorgrafts to characterize driver mutations in fast- and slow-growing subgroups. RESULTS: An engraftment rate of 71.7% (43/60) was achieved, substantially exceeding rates reported in prior studies. Clinical characteristics were independent of engraftment success and outgrowth time (all p > 0.05). Fast- and slow-growing tumorgrafts diverged in frequently altered genes: KMT2C, APOB, CDK12 and MSH2 predominated in fast-growing grafts, whereas TP53, CHD3 and TET2 were enriched in slow-growing grafts. Slow-growing tumorgrafts correlated with longer progression-free survival (p = 0.02). PDX-guided treatment was associated with improved prognosis. CONCLUSIONS: Intramuscular transplantation into NCG mice yields high engraftment rates for GC PDX. PDX-guided chemotherapy selection is associated with favorable outcomes. Driver mutation divergence between fast- and slow-growing tumorgrafts provides candidate prognostic biomarkers.

Animals↗

PubMed2026

Eco-evolutionary dynamics sustain a potent yet rare antibiotic gene cluster in Streptomyces.

Microbial secondary metabolites have been recognized and utilized for nearly a century. Nevertheless, the eco-evolutionary mechanisms governing their distribution among microorganisms remain largely unresolved. In this study, we examined intraspecific interactions within Streptomyces albidoflavus and identified a strain exhibiting potent antagonistic activity against conspecifics. This "killer" phenotype was attributed to the production of kosinostatin, a hybrid aromatic polyketide antibiotic. Evolutionary genomic analyses provided strong evidence that the kosinostatin biosynthetic gene cluster was horizontally acquired in S. albidoflavus over a relatively short evolutionary timescale, a finding consistent with its sparse distribution within this species, across the genus Streptomyces, and even throughout the phylum Actinomycetota. Using microcosm assays, we demonstrated that the kosinostatin producer outcompeted sensitive conspecifics in liquid culture but not in soil, indicating that environmental context plays a key role in altering the fitness benefits of this cluster. Moreover, the competitive advantage was observed only in the presence of sensitive strains, revealing a trade-off between fitness benefits and metabolic costs. These results highlight the role of context-dependent selection in shaping the evolutionary persistence of the kosinostatin cluster. The current distribution pattern of this cluster in S. albidoflavus likely results from a dynamic interplay of intraspecific horizontal gene transfer, vertical inheritance, and recurrent gene loss. Overall, our findings establish an eco-evolutionary framework that explains the rarity of a potent antibiotic gene cluster in Streptomyces, illustrating how environmental constraints, fitness trade-offs, and gene flux collectively orchestrate the biosynthetic architecture of Streptomyces species.

Streptomyces↗

PubMed2025

Optimized genomic editing of a common Duchenne muscular dystrophy mutation in patient-derived muscle cells and a new humanized mouse model.

Duchenne muscular dystrophy (DMD) is a fatal X-linked, recessive disease caused by mutations in the DMD gene encoding dystrophin, a membrane-associated protein necessary for maintaining muscle structure and function. One of the common DMD mutations is the deletion of exon 52 (Δ52), which introduces a premature stop codon in exon 53, preventing the expression of functional dystrophin protein. Patients with this mutation could benefit from skipping or reframing exon 53 to restore the dystrophin open reading frame. In this study, we investigated the efficacy of single-cut CRISPR gene editing with Staphylococcus pyogenes Cas9 (SpCas9)-LRVQR to restore dystrophin expression in patient-derived induced pluripotent stem cells (iPSCs) and a newly generated humanized DMD mouse model. We compared two injection routes for adeno-associated virus (AAV) serotype 9 to deliver gene-editing components to neonatal mice: intraperitoneal (IP) and facial vein (FV) injection. We observed efficient restoration of dystrophin protein expression across multiple skeletal muscle groups and the heart. The AAV9-mediated CRISPR single-cut approach ameliorated key DMD hallmarks, including histopathological phenotypes, impaired grip strength, and elevated serum creatine kinase levels. Our optimized strategies for dystrophin restoration in humanized DMD mice with exon 52 deletion represent a promising treatment for DMD.

AAV↗

PubMed2025

CAUSAL ASSOCIATION BETWEEN SEPSIS AND FIBROBLAST GROWTH FACTORS AS WELL AS THEIR RECEPTORS LEVELS: A TWO-SAMPLE MENDELIAN RANDOMIZATION STUDY.

Objective: The potential association between sepsis risk and circulating levels of fibroblast growth factors (FGFs) and their receptors (FGFRs) has been a focus of research; however, the causal relationship between them remains to be elucidated. We hypothesize a causal association between genetically predicted FGFs, FGFRs, and sepsis risk, and we conduct a Mendelian randomization (MR) study to validate this hypothesis. Methods: We utilized a two-sample MR design to assess the effect of genetic variants associated with various FGFs (FGF1, FGF2, FGF7, FGF16, FGF19, FGF21, FGF23, FGF5) and FGFRs (FGFR1, FGFR2, FGFR3, α-Klotho) on sepsis risk, using genome-wide association study summary statistics. Our MR analyses employed the inverse-variance weighted (IVW) method, along with weighted median, weighted mode, and MR-Egger regression, supplemented by sensitivity analyses to ensure robustness. Results: The MR analysis identified an unequal number of instrumental variables ranging from 2 to 17 for FGFs and FGFRs when sepsis was the outcome. No significant correlation was found between genetically determined FGF levels and sepsis risk by IVW analysis (all P > 0.05). Correspondingly, similar nonsignificant associations were observed for FGFRs (all P > 0.05). Other MR methods corroborated the IVW findings. Sensitivity analyses, including Cochran's Q test, MR-Egger, and MR pleiotropy residual sum and outlier, indicated no significant heterogeneity or pleiotropy in the relationships, with the exception of a nonsignificant correlation between FGFR1 and sepsis that persisted after the exclusion of an outlier (odds ratio, 0.84; P = 0.34). Conclusion: The analysis found no significant causal associations between FGFs, their receptors, and sepsis risk, indicating a need for further research on their complex interactions.

Humans↗

PubMed2024

Effect of light on ascorbic acid biosynthesis and bioinformatics analysis of related genes in Chinese chives.

Ascorbic acid (AsA) is an essential nutritional component and powerful antioxidant in vegetables, and in plants, AsA levels are regulated by light. AsA levels in the leaves of Chinese chive (Allium tuberosum Rottler ex Spr), a popular vegetable, are poorly understood. Thus, this study was performed to assess the influence of light on AsA biosynthesis in chive and select related genes (AtuGGP1 and AtuGME1); in addition, bioinformatic analyses and gene expression level assays were performed. The biological information obtained for AtuGGP1 and AtuGME1 was analysed with several tools, including NCBI, DNAMAN, and MEGA11. After different light treatments were performed, the Chive AsA content and AtuGGP1 and AtuGME1 expression levels were determined. These results suggest that 1) compared with natural light, continuous darkness inhibited AsA synthesis in chives. 2) The amino acid sequences of AtuGGP1 and AtuGME1 are very similar to those of other plants. 3) The trends observed for the expression levels of AtuGGP1 and AtuGME1 were consistent with the AsA content observed in chives. Hence, we speculated that light controls AsA biosynthesis in chives by regulating AtuGGP1 and AtuGME1 expression. This study provided impactful and informative evidence regarding the functions of GGP and GME in chives.

Ascorbic Acid↗

PubMed2023

Single-swap editing for the correction of common Duchenne muscular dystrophy mutations.

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disease of progressive muscle weakness and wasting caused by the absence of dystrophin protein. Current gene therapy approaches using antisense oligonucleotides require lifelong dosing and have limited efficacy in restoring dystrophin production. A gene editing approach could permanently correct the genome and restore dystrophin protein expression. Here, we describe single-swap editing, in which an adenine base editor edits a single base pair at a splice donor site or splice acceptor site to enable exon skipping or reframing. In human induced pluripotent stem cell-derived cardiomyocytes, we demonstrate that single-swap editing can enable beneficial exon skipping or reframing for the three most therapeutically relevant exons-DMD exons 45, 51, and 53-which could be beneficial for 30% of all DMD patients. Furthermore, an adeno-associated virus delivery method for base editing components can efficiently restore dystrophin production locally and systemically in skeletal and cardiac muscles of a DMD mouse model containing a deletion of Dmd exon 44. Our studies demonstrate single-swap editing as a potential gene editing therapy for common DMD mutations.

AAV↗

PubMed2007

Interactions of cyclosporin a with breast cancer resistance protein.

The objective of this study was to investigate whether cyclosporin A (CsA) is a modulator for breast cancer resistance protein (BCRP). The interactions between CsA and BCRP were evaluated by using both membrane- and cell-based assays. CsA inhibited BCRP or BCRP R482T mutant-associated ATPase with an IC(50) of 26.1 and 7.3 microM (31,388 and 8779 ng/ml), respectively, indicating that CsA is a modulator for BCRP and its R482T mutant. The apparent permeability (P(app)) of CsA was not affected by the BCRP-specific inhibitor Ko143 in both apical-to-basolateral (A-to-B) and basolateral-to-apical (B-to-A) directions in hBCRP- or mBcrp-transfected MDCKII cells, whereas CsA at 50 microM significantly increased the A-to-B transport and decreased B-to-A transport of BCRP substrates, [(3)H]estrone-3-sulfate ([(3)H]E3S) and [(3)H]methotrexate ([(3)H]MTX), in hBCRP- and mBcrp1-trasfected MDCKII cells. Similar to cellular transport studies, CsA did not exhibit ATP-dependent uptake in BCRP-expressed membrane vesicles but inhibited the ATP-mediated E3S and MTX uptake in the same vesicles. The inhibitory constant (K(i)) of CsA toward BCRP was 6.7 microM (8507 ng/ml) and 7.8 microM (9380 ng/ml) when using E3S or MTX, respectively, as a BCRP substrate. The inhibitory potency of CsA on BCRP wild type or its R482T mutant was lower than that on P-glycoprotein. The present studies demonstrate that CsA is an inhibitor but not a substrate for BCRP, and has low potential to cause drug-drug interactions with BCRP substrate drugs due to its weak inhibitory effect on BCRP and BCRP R482T mutant at its normal therapeutic blood concentrations (200-400 ng/ml) (Blood 91:362-363, 1998).

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2007

Actin deficiency induces cofilin phosphorylation: proteome analysis of HeLa cells after beta-actin gene silencing.

Actin-binding proteins regulate the dynamic structure and function of actin filaments in the cell. Much is known about how manipulation of the actin-binding proteins affects the structure and function of actin filaments; however, little is known about how manipulation of actin in the cell affects actin-binding proteins. We addressed this question by utilizing two technologies: RNA interference and 2-dimensional gel electrophoresis. We knocked down beta-actin expression in HeLa cells using short interfering RNA and applied 2-DGE to examine alterations in the HeLa cell proteome. We revealed a 2-5 fold increases of four protein spots on 2-D gels and identified these proteins by mass spectrometry. Three of the four proteins were actin-binding proteins, including cofilin, which promotes both disassembly and assembly of actin filaments but becomes inactivated when phosphorylated. Further examination revealed that the cofilin total protein level barely increased, but the phosphorylated cofilin level increased dramatically in HeLa cells after beta-actin siRNA treatment. These results suggest that in response to siRNA-induced beta-actin deficiency HeLa cells inactivate cofilin by phosphorylation rather than down-regulate its protein expression level. This study also demonstrates that the combination of RNA interference and 2-dimensional gel electrophoresis technologies provides a valuable method to study protein interactions in a specific cellular pathway.

Actin Depolymerizing Factors↗

PubMed2006

Angiotensin II receptor blockade ameliorates mesangioproliferative glomerulonephritis in rats through suppression of CTGF and PAI-1, independently of the coagulation system.

BACKGROUND: Previously we observed that the coagulation system promotes matrix protein accumulation through transforming growth factor (TGF)-beta and connective tissue growth factor (CTGF) expression in rat mesangioproliferative glomerulonephritis (MsPGN). Angiotensin II receptor blockers (ARBs) are known to suppress matrix accumulation in experimental MsPGN. In the present study, we investigated whether ARB suppresses MsPGN through inhibition of these profibrotic cytokines, and in relation to coagulation and fibrinolytic systems. METHODS: MsPGN was induced in Wistar rats by intravenous injection of anti-Thy-1.1 monoclonal antibody, OX-7. As an ARB, olmesartan was orally administered in rat feed from the day of OX-7 injection (day 0) to day 8, when rats were sacrificed and kidney specimens were collected. The degrees of cellular proliferation, matrix production, coagulation factors, and inhibitory factor of fibrinolysis were evaluated. RESULTS: Although blood pressure did not change in the normal, disease control, or treatment groups, the amount of urinary protein was significantly decreased in the ARB-treated groups, compared with the disease control group (p < 0.05). alpha-Smooth muscle actin expression was suppressed significantly in the treatment groups (p < 0.001). Blue-staining areas of trichrome, the number of proliferating cell nuclear antigen (PCNA)- or ED-1-positive cells, fibronectin and plasminogen activator inhibitor type 1 in glomeruli significantly decreased in the treatment groups (p < 0.05, respectively); however, fibrin-related antigen and factor V depositions were not suppressed in the treatment groups. CONCLUSIONS: These results suggest that the ARB drug would ameliorate MsPGN in vivo, at least partly through CTGF and plasminogen activator inhibitor type 1 suppression, and independently of the local coagulation system in glomeruli.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2006

Roles of coagulation pathway and factor Xa in rat mesangioproliferative glomerulonephritis.

Tissue factor initiates the extrinsic coagulation pathway by activating coagulation factor X to factor Xa, and factor V is a cofactor for the prothrombin activation by factor Xa. As factor Xa is known to promote the proliferation of mesangial cells in culture, the roles of the coagulation pathway and factor Xa were studied in an animal model of mesangioproliferative glomerulonephritis (MsPGN). MsPGN was induced in Wistar rats by an intravenous injection of anti-Thy 1.1 monoclonal antibody, OX-7. To clarify the role of factor Xa in MsPGN, a specific factor Xa inhibitor, DX-9065a, was injected intravenously at 2.5 or 10 mg/kg at the same time as OX-7, and kidney involvement was assessed by immunohistological analyses. We also examined p44/42 mitogen-activated protein (MAP) kinase activation. Time-course study revealed that expressions of tissue factor, factor V, and protease-activated receptor 2 (PAR2) were peaked on day 3, followed by factor X accumulation and mesangial proliferation. DX-9065a treatment significantly ameliorated proteinuria in a dose-dependent manner on day 8. Histological analyses showed a significant reduction in the size of glomeruli, the total number of glomerular cells, and crescent formation by DX-9065a treatment. Macrophage infiltration, which was rapidly observed on day 1 in disease control rats was not inhibited on days 1-3 by DX-9065a treatment, however it was suppressed on days 5-8. The deposition of fibrin, the number of PCNA-positive cells, and phosphorylation of p44/42 MAP kinase were markedly increased in the disease control group, whereas they were significantly reduced in the treatment group. Tissue factor and factor V induction may accelerate MsPGN through the activation and accumulation of factor X via proinflammatory and procoagulant mechanisms, and the inhibition of factor Xa would be a promising method to regulate the disease process.

Analysis of Variance↗

PubMed2006

Immunologic analysis induced by DNA vaccine encoding E protein of Beijing-1 strain derived from Japanese encephalitis virus.

OBJECTIVE: We have compared the gene expression and DNA immunization efficacy encoding prME and E proteins of a different strain (JaGAr-01) derived from Japanese encephalitis virus. This study aimed to construct a recombinant encoding E protein of the Beijing-1 strain derived from Japanese encephalitis virus and analyze the humoral, cellular and protective immunity induced by the above recombinant. METHODS: The recombinant pJBE containing E (1,500 bps) gene from the Beijing-1 strain of Japanese encephalitis virus was constructed and then transfected into the HepG2 cell line by liposome fusion. The expression of E (about 53 kD) protein in transfected cells was analyzed by Western blot using a specific anti-JEV-E antibody. BALB/c mice were vaccinated with 3 microg of pJBE by the gene-gun technique. JaGAr-01 and Beijing-1 strains (10(5) PFU/100 microl) of Japanese encephalitis virus were given to BALB/c mice by intraperitoneal injection 3 weeks after double DNA immunization with a lethal virus challenge. BALB/c mice were observed for 21 days after challenge. An 80% plaque reduction neutralization test was performed to titrate the neutralization antibody before and after viral challenge. A lactate dehydrogenase activity release test was used to examine cytotoxic T lymphocyte activity after double DNA immunization. RESULTS: The expression of about 53 kD protein associated with pJBE was determined in transfected HepG2 cells with specific anti-JEV-E antibody. A higher level of neutralization antibodies and the cytotoxicity effect were induced with pJBE immunization using the gene-gun technique, and were similar to those induced with inactivated vaccine derive from the Beijing-1 strain of Japanese encephalitis virus. Balb/c mice immunized with pJBE survived the challenge with the different strains of Japanese encephalitis virus; however, Balb/c mice immunized with inactivated vaccine did not survive the challenge with the JaGAr-01 strain of Japanese encephalitis virus at all. CONCLUSIONS: DNA vaccine containing the E protein gene derived from Japanese encephalitis virus can provide not only better efficacy including humoral and cellular immunity, but also cross-protection against infection with homologous and heterologous Japanese encephalitis virus.

Animals↗

PubMed2006

A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure.

Diverse forms of injury and stress evoke a hypertrophic growth response in adult cardiac myocytes, which is characterized by an increase in cell size, enhanced protein synthesis, assembly of sarcomeres, and reactivation of fetal genes, often culminating in heart failure and sudden death. Given the emerging roles of microRNAs (miRNAs) in modulation of cellular phenotypes, we searched for miRNAs that were regulated during cardiac hypertrophy and heart failure. We describe >12 miRNAs that are up- or down-regulated in cardiac tissue from mice in response to transverse aortic constriction or expression of activated calcineurin, stimuli that induce pathological cardiac remodeling. Many of these miRNAs were similarly regulated in failing human hearts. Forced overexpression of stress-inducible miRNAs was sufficient to induce hypertrophy in cultured cardiomyocytes. Similarly, cardiac overexpression of miR-195, which was up-regulated during cardiac hypertrophy, resulted in pathological cardiac growth and heart failure in transgenic mice. These findings reveal an important role for specific miRNAs in the control of hypertrophic growth and chamber remodeling of the heart in response to pathological signaling and point to miRNAs as potential therapeutic targets in heart disease.

Animals↗

PubMed2006

Characterization and expression of a new subfamily member of penaeidin antimicrobial peptides (penaeidin 5) from Fenneropenaeus chinensis.

Penaeidins are members of a special family of antimicrobial peptides existing in penaeid shrimp and play an important role in the immunological defence of shrimp. Here, we report one penaeidin with a putative isotype newly cloned from fleshy prawn Fenneropenaeus chinensis. The penaeidin open reading frame encodes a 79 amino acid peptide while two exons and an intron were identified within the 1126bp genomic sequence of Fenchi-penaeidin 5. Phylogenetic analysis and sequence comparison with other known penaeidins suggest the new gene belongs to a novel subfamily of penaeidins and the two isoforms were named Fenchi-penaeidin 5-1 and 5-2, respectively. Fenchi-penaeidin 5 mRNA was examined in normal and microbial challenged shrimp and was found to be constitutively expressed in heamocytes, heart, gill, intestine and ovary. Bacterial challenge resulted in mRNA up-regulation, inducing expression in hepatopancreas and stomach. Fenchi-penaeidin 5-1 was also expressed in Pichia pastoris, and recombinant Fenchi-penaeidin 5-1 exhibited activities against Gram-positive and -negative bacteria and fungi.

Amino Acid Sequence↗

PubMed2006

Coactivator control of cardiovascular growth and remodeling.

Transcriptional coactivators enhance gene expression by associating with sequence-specific transcription factors and serve as the primary targets of developmental and physiological signals in diverse biological processes. Recent studies have revealed key roles for transcriptional coactivators in the control of gene expression during development, growth and remodeling of the cardiovascular system. Based on the importance of the cardiovascular coactivators identified to date, coactivator control is emerging as a central regulatory mechanism in development and homeostasis of the cardiovascular system and other tissues.

Animals↗

PubMed2006

Constructing a novel Nanodevice powered by delta-free FoF1-ATPase.

A Nanodevice was constructed by delta-free F(o)F(1)-ATPase within chromatophores and actin filaments through biotinlipid-streptavidin-biotin-(AC(5))(2)Sulfo-OSu system. One actin filament linking with many chromatophores functions as the Nanodevice body and many delta-free F(o)F(1)-ATPase as the Nanodevice motors. Movement of the Nanodevice was observed directly by fluorescence microscopy with CCD camera after illumination. The moving speed was about 2.17-24.43mum/s for various length Nanodevices and most of them were stopped by adding CCCP. This means that the Nanodevice was driven by PMF (proton-motive force) in the cooperating delta-free F(o)F(1)-ATPase. From bioengineering point of view, the cooperation of F(o)F(1)-ATPase is a very important research field in the future.

Actins↗

PubMed2006

Ectopic expression of ThCYP1, a stress-responsive cyclophilin gene from Thellungiella halophila, confers salt tolerance in fission yeast and tobacco cells.

The halophyte Thellungiella halophila (salt cress) is an ideal model system for studying the molecular mechanisms of salinity tolerance in plants. Herein, we report the identification of a stress-responsive cyclophilin gene (ThCYP1) from T. halophila, using fission yeast as a functional system. The expression of ThCYP1 is highly inducible by salt, abscisic acid (ABA), H(2)O(2) and heat shock. Ectopic overexpression of the ThCYP1 gene enhance the salt tolerance capacity of fission yeast and tobacco (Nicotiana tabacum L.) cv. Bright Yellow 2 (BY-2) cells significantly. ThCYP1 is expressed constitutively in roots, stems, leaves and flowers, with higher expression occurring in the roots and flowers. The ThCYP1 proteins are distributed widely within the cell, but are enriched significantly in the nucleus. The present results suggest that ThCYP1 may participate in response to stresses in the salt cress, perhaps by regulating appropriate folding of certain stress-related proteins, or in the signal transduction processes.

Abscisic Acid↗

PubMed2006

Modeling competitive reaction mechanisms of peroxynitrite oxidation of guanine.

5-Guanidino-4-nitroimidazole is a stable product from the peroxynitrite induced one-electron oxidation of guanine. Reaction mechanisms to form the 5-guanidino-4-nitroimidazole as well as 8-nitroguanine, through the combination of the guanine radical cation and nitrogen dioxide radical and through the combination of the deprotonated neutral guanine radical and nitrogen dioxide radical, have been investigated by the use of the B3LYP method of density functional theory. Our calculations suggest that the guanine radical cation mechanism is preferred over the neutral guanine radical mechanism and that a water molecule is involved in the reaction as a catalyst or as a reactant.

Cations↗

PubMed2006

Overexpression of sorcin in multidrug resistant human leukemia cells and its role in regulating cell apoptosis.

In an attempt to identify novel proteins involved in the emergence of multidrug resistance (MDR) in leukemia cells, we adopted a proteomics approach to analyze protein expression patterns in leukemia cell lines, K562, and its MDR counterpart, K562/A02. Combining high-resolution two-dimensional gel electrophoresis and mass spectrometry, we compared the protein expression profiles between K562 and K562/A02. A total number of 22 protein spots with altered abundances of more than 2-fold were detected and 14 proteins were successfully identified. Consistent with our previous observations by cDNA microarray, sorcin, a 22-kDa calcium-binding protein, was also identified by this proteomic approach with a 10.4-fold up-regulation in K562/A02 cells. Overexpression of sorcin protein in K562 cells by gene transfection led to significantly reduced cytosolic calcium level and increased resistance to cell apoptosis. Further, leukemia cell lines over-expressing sorcin also showed up-regulation of Bcl-2, along with decreased level of Bax. Taken together, our results suggest that sorcin plays an important role in the emergence of MDR in leukemia cells via regulating cell apoptosis pathways, thus may represent both a new MDR marker for prognosis and a good target for anti-MDR drug development.

Antineoplastic Agents, Phytogenic↗