Biomedical subjects

Motohiro Ohkoshi

Publications and source records attributed to Motohiro Ohkoshi.

3 recordsLinked to original sources

PubMed2002

Decrease in growth factor receptors after treatment with serine protease inhibitor ONO-3403.

FOY-305 is a synthetic serine protease inhibitor and ONO-3403 is a derivative with a higher protease-inhibitory activity. The growth-suppressive effects of ONO-3403 were more prominent in Ha-ras-transformed NIH3T3 (ras-NIH) cells than in non-transformed NIH3T3 cells. After treatment of ras-NIH cells with ONO-3403 at 100-200 microg/ml, the percentage of cells found in G(1) phase decreased and, concomitantly, that in S phase increased. Molecular events caused by ONO-3403 were investigated by Western blot analysis using anti-phosphotyrosine antibody. The results showed a marked decrease in the tyrosine phosphorylation level of a 180-kDa protein after treatment with ONO-3403. This 180-kDa phosphotyrosine-containing molecule which was tentatively designated pY-p180 might be platelet-derived growth factor (PDGF) receptor since addition of PDGF to serum-starved NIH3T3 cells induced a marked tyrosine phosphorylation of the same size within 5 min. This was further confirmed by immunoprecipitation of cell extract with anti-PDGF-receptor antibody followed by Western blot analysis using anti-phosphotyrosine antibody. Treatment of T.Tn human esophageal carcinoma cells with ONO-3403 caused also decrease in pY-p180, which appeared to be epidermal growth factor receptor. Thus, ONO-3403 may induce growth suppression by down-regulation of cell surface growth factor receptors.

3T3 Cells↗

PubMedDate not supplied

Growth inhibition of mouse autochthonous skin cancer by oral administration of new serine protease inhibitor ONO-3403.

The orally active serine protease inhibitor ONO-3403 is an analog of FOY-3403 that has more potent protease-inhibitory activity. In the present study, oral administration of ONO-3403 was used to challenge 3-methylcholanthrene-induced carcinoma. This drug was administered 3 times daily for 9 weeks via a stomach tube at a dose of 10 mg/kg in a 1-ml volume in 6 mice harboring solid tumors. This protease inhibitor significantly inhibited tumor growth (p<0.001) and prolonged survival-time (p<0.01). These results indicated that oral administration of the potent serine protease inhibitor ONO-3403 has an antitumor effect on malignant tumors.

Administration, Oral↗

PubMedDate not supplied

Antimetastatic activity of a synthetic serine protease inhibitor, FOY-305 (Foypan).

Metastasis is one of the major causes of mortality in cancer. It is well known that the activities of cell surface serine proteases are especially enhanced in malignant tumors. Proteolytic degradation of the extracellular matrix and basal membrane is a crucial event for tumor cell invasion and metastasis formation. FOY-305 (Foypan), a remedy for tumor pancreatitis, is a broad spectrum synthetic serine protease inhibitor which inhibits enzymatic activities including trypsin, thrombin, kallikrein and plasmin. Using Lewis lung carcinoma cell, we found that FOY-305 inhibited both spontaneous and experimental pulmonary metastasis. Furthermore, the combined treatment of FOY-305 and a traditional anti-cancer drug, 5-FU or bleomycin, resulted in marked enhancement of anti-pulmonary metastatic activity.

Animals↗