Enhancement of antitumor effect by intratumoral administration of bax genein combination with anticancer drugs in gastric cancer

Proapototic gene is an important target to enhance the chemotherapeutic eff ect in cancer cells. Based on in vitro study showing that the introduction of bax gene enhanced the sensitivity to anticancer drugs, we examined wheth er the intratumoral administration of bax; gene could enhance the antitumor effect in combination with anticancer drugs in gastric cancer. The human g astric cancer cell line, MKN45 was transplanted into nude mice, and the int ratumoral administration of bax gene was performed using the bax cDNA plasm id complexed with a cationic lipopolyamine. The enhancement of antitumor ef fect was examined in the combination with 5-fluorouracil (5-FU) and cisplat in (CDDP). The anticancer drugs were administered intraperitoneally with on e third of LD,, four times at 4-day intervals, and the antitumor effect was assessed by the NCI protocol. The expression of bax gene was analyzed by R T-PCR and the apoptotic cell death was assessed by TUNEL method. The intrat umoral administration of bax gene alone showed slight anti-tumor effect as compared to that of control tumor injected with vector alone. The antitumor effect of 5-FU and CDDP was significantly enhanced in the combination with intra-tumoral administration of bax gene as compared to that of CDDP and 5 -FU alone (p<0.05, Student's t-test). The enhancement of antitumor effect w as associated with the constitutive overexpression of bax gene and with the induction of apoptosis in the tumor treated with anticancer drug and bax g ene. These results indicate that the combination therapy of intratumoral ad ministration of bax gene complexed with a cationic lipopolyamine and antica ncer drugs may provide us a new strategy for cancer chemotherapy to enhance its therapeutic efficacy in gastric: cancer as termed with gene chemothera py.