Biomedical subjects

Xian Zhong

Publications and source records attributed to Xian Zhong.

6 recordsLinked to original sources

PubMed2006

The Helicobacter pylori virulence factor CagA promotes Erk1/2-mediated Bad phosphorylation in lymphocytes: a mechanism of CagA-inhibited lymphocyte apoptosis.

The Helicobacter pylori virulence factor, CagA, is causally linked to lymphoma of gastric mucosa-associated lymphoid tissue (MALT). However, it is unclear how CagA promotes the development of gastric MALT lymphoma. We investigated whether CagA modulates the activation of Erk1/2 and their downstream apoptosis regulators in B lymphocytes. Transfection of B1 lymphocytes with cagA transiently increased Erk1/2 phosphorylation, which was negatively regulated by MKP-1 and MKP-6. Activation of Erk1/2 led to phosphorylation of Bad at Ser-112, as confirmed with a chemical Erk1/2 inhibitor. However, CagA-induced Erk1/2 activation did not alter expression of either Bcl-2 or Bax. Importantly, cagA-transfected B1 cells were significantly protected against apoptosis induced by hydroxyurea. Our results reveal that CagA, to some extent like IL-3, can enhance lymphocytes' ability to evade apoptosis through phosphorylation of Bad. This may account, at least in part, for the ability of CagA to promote lymphomagenesis.

Amino Acid Motifs↗

PubMed2006

Silymarin causes caspases activation and apoptosis in K562 leukemia cells through inactivation of Akt pathway.

Cancer is one of the largest causes of death in both men and women. Akt, overexpressed in a number of human malignancies including leukemia, is an important target in cancer prevention and/or therapy. Silymarin, a flavonoid antioxidant, has high human acceptance being used clinically for the treatment of liver diseases. In this study, Akt activity was inhibited by silymarin without changes in total Akt level associated with a prominent caspases-9 and -3 activation as well as PARP cleavage, accompanied by a strong apoptotic death and growth inhibition of K562 cells. These findings suggest that silymarin could serve as a candidate for anti-leukemia drug.

Antioxidants↗

PubMed2005

Transformed immortalized gastric epithelial cells by virulence factor CagA of Helicobacter pylori through Erk mitogen-activated protein kinase pathway.

CagA of Helicobacter pylori is a protein that has been closely associated with gastric cancer and that can intervene with signal pathways in cells. Its precise relationship with the occurrence of gastric cancer, however, remains unclear. The purpose of this study is to investigate whether CagA can promote transformation of normal gastric epithelial cells and to consider via what mechanisms CagA may exert its effects. Transformed colonies were merged in soft-agarose medium after immortalized gastric epithelial cells were transfected with recombinant pLHCX retrovirus with cagA and/or dimethylhydrazine. The number of transformed colonies in the group containing cagA/pLHCX retrovirus, combined with a subthreshold dose of dimethylhydrazine, was more than that for cagA/pLHCX retrovirus or dimethylhydrazine at a subthreshold dose alone. For cagA-transfected cells, only IQGAP-2, R-Ras and B-Raf of the Ras/mitogen-activated protein kinase signal pathway were markedly increased, and the activity of extracellular signal-regulated kinase 1/2 (Erk1/2) kinase was significantly higher than that in dimethylhydrazine-transformed cells or control cells. However, no evidence of alteration of any other molecules of the Ras superfamily was observed in cagA-transfected cells. These findings suggest that CagA can transform gastric epithelial cells through activation of the Erk1/2 pathway; this mechanism may, however, be independent of Ras activation.

Cell Line↗

PubMed2005

Transformation of immortalized colorectal crypt cells by microcystin involving constitutive activation of Akt and MAPK cascade.

It has been shown by epidemiological and animal studies that microcystin is an important exogenous factor involved in the carcinogenesis of colorectal cancer (CRC). However, details of the mechanism remain unclear. Transformation of colorectal cells is an important initial step in carcinogenesis. Whether microcystin is capable of transforming immortalized colorectal crypt cells, and what the mechanism might be, was investigated. In the present study, we demonstrated that immortalized colorectal crypt cells could be transformed by microcystin. Transformed colorectal crypt cells showed an anchorage-independent growth phenotype, and the proliferation activities of microcystin-transformed cells were also greater than that of immortalized colorectal crypt cells. The Akt and the p38, JNK of mitogen-activated protein kinase (MAPK) pathways in microcystin-transformed cells were found to be constitutively activated. In microcystin-transformed cells, PI3K, MAPKAPK2, Akt, cyclin D1 and cyclin D3 in the Akt pathway; IQGAP-2, RabGTPase, Rap1GAP, RasGAP, R-Ras, Krev-1 and TC21 of the Ras GTP/GDP protein family; and A-Raf, B-Raf and PAK in the Ras/MAPK pathway were all markedly upregulated. However, in positive control cells, dimethylhydrazine-transformed cells, only the Akt pathway was activated by PI3K, and no evidence of alteration of any molecules of the Ras superfamily was observed. Inhibition of Akt, p38 and JNK activation led to a reduced proliferation of microcystin-transformed cells. This implies that the constitutive activation of Akt and the p38, JNK of MAPK pathways in microcystin-transformed cells may be the mechanism by which this important external factor acts in the carcinogenesis of CRC.

Cell Culture Techniques↗

PubMed2005

[Effect of Kanglaite injection oncyclooxygenase activity in lung carcinoma A549 cell].

OBJECTIVE: To study the effect of Kanglaite injection on cyclooxygenase activity in lung carcinoma A549 cells. METHODS: The expression of mRNA of COX-1 and COX-2 were measured by RT-PCR. The expression of COX-2 protein was measured by Western-blot. RESULT: Kanglaite injection could selectively decreased COX-2 mRNA expression and protein expression while COX-1 mRNA expression was unchanged. CONCLUSION: Kanglaite injection is selectively inhibitory agent of COX-2, and possess inhibitory effects on cyclooxygenase 2.

Antineoplastic Agents, Phytogenic↗

PubMed2004

[Conditionally immortalized human colorectal crypt cell line].

OBJECTIVE: To establish human colorectal crypt cell line. METHODS: Colorectal crypt cells were separated from human fetal gut by dispase I digestion, AKP-negative cells from fetal colorectal crypt were collected and cultured on Matrigel matrix. Subsequently the primary cultured cells were transfected with recombinant retrovirus containing human telomerase reverse transcriptase (hTERT) and simian virus 40 large T antigen (SV40 LT) in 48 h. The characterization of immortalized cells was identified after the transfection and cells were screened with antibiotics for 12 approximately 16 weeks and expanded. RESULTS: Mucin, cytokeratin-pan, 8, 19 were presented in immortalized cells by immunohistochemical staining; ectopic expressions of both hTERT and SV40 LT were also found in immortalized cells by Western blotting. Agarose electrophoresis showed that the cells expressed Musashi-1 mRNA. No evidence of carcinogenesis was found in nude mouse experiment and soft-agarose cloning test. CONCLUSION: The immortalized human colorectal crypt cells were characterized and the established cell line may be an ideal target for carcinogenesis study in vitro.

Cell Line, Transformed↗