Enhancement of chemotherapeutic agents induced-apoptosis associated with activation of c-Jun N-terminal kinase 1 and caspase 3 (CPP32) in bax-transfected gastric cancer cells

Apoptois is an important determinant in the sensitivity to chemotherapeutic agents in gastric cancer cells. In this study, we examined whether the int roduction of the bar gene into MKN45 gastric cancer cells could enhance the sensitivity to chemotherapeutic agents in association with apoptosis. Apop tosis in the bax-transfected gastric cancer cells was enhanced following th e treatment of various chemotherapeutic agents including adriamycin (ADM), cisplatin (CDDP), etoposide (VP-16) and taxotere (TXT) as compared to those of neo gene-transfected cells. The enhancement of apoptosis was coincident with the increase of sensitivity in the ratio of IC50 value, that was 1.3- fold in ADM, 4.4-fold in CDDP, 4.6-fold in VP-16 and 2.5-fold in TXT, respe ctively. Further, the enhancement of apoptosis in the bax-transfected gastr ic cancer cells was associated with the activation of c-Jun N-terminal kina se 1 (JNK I) and caspase 3 (CPP32). The increases of sensitivities to these agents in the bax-transfected cells were also demonstrated in in vivo expe riments using the tumor cells transplanted into nude mice. The tumor growth in the bax-transfected cells was significantly suppressed following the tr eatment of CDDP or VP-16 compared to that of neo-transfected cells (p<0.05) . These results indicated that, the bar gene might play a critical role in determination of sensitivity to chemotherapeutic agent in gastric cancer ce lls in vivo, and that the activation of JNK I and CPP32 might Be involved i n the signal transduction pathways leading to apoptosis.