PACLITAXEL-INDUCED APOPTOSIS IN HUMAN GASTRIC-CARCINOMA CELL-LINES

BACKGROUND. Gastric cancer is one of the most common cancers in Asia. Chemotherapy and radiation therapy have had limited success. Recently, paclitaxel has been found to be effective against a variety of cancer s, including lung, breast, ovary, melanoma, and prostate. Whether pacl itaxel is effective in the treatment of gastric cancer is not known an d is worthy of investigation. METHODS. Human gastric carcinoma cell li nes NUGC-3 and SC-M1 were examined for response to paclitaxel treatmen t. Cancer cells were treated with paclitaxel (0.001, 0.01, 0.1, and 1 mu M) for 1-3 days. Cell number was counted by hemocytometer and cell viability was determined by the trypan blue exclusion method. Cell cyc le progression and expression of proliferating cell nuclear antigen (P CNA) were examined by flow cytometry. The percentage of apoptotic cell s was determined after staining with hematoxylin and eosin. RESULTS. P aclitaxel was cytotoxic to the two human gastric carcinoma cell lines examined. The growth-inhibiting dose was 0.01 mu M. Paclitaxel-treatcd gastric carcinoma cells were arrested mainly in G(2)/M phases before apoptosis. However, treatment with 0.01 mu M of paclitaxel resulted in a decrease of cells at G(0)/C-1 phases without an increase of cells a t G(2)/M phase indicating that paclitaxel was also cytotoxic to gastri c carcinoma cells at G(0)/G(1) phases. In addition, the expression of PCNA was significantly increased in 0.1 and 1 mu M paclitaxel-treated cells, suggesting that DNA repair was increased in these cells. CONCLU SIONS. Paclitaxel is effective in growth inhibition of gastric carcino ma cell lines in clinically attainable concentrations. Our results sug gest that paclitaxel is a potential chemotherapeutic drug for gastric carcinoma. (C) 1996 American Cancer Society.