Activation and the interaction of proapoptotic genes in modulating sensitivity to anticancer drugs in gastric cancer cells

Taxotere (Docetaxel) is a novel microtubulin inhibitor which is currently i n phase II/III clinical trial. We found that the sensitivity to taxotere wa s corrected with apoptotic cell death determined by the internucleosomal DN A ladders in gastric cancer cell lines. The treatment of taxotere activated proapoptotic genes such as bcl-Xs and bax genes. The relationship between the mRNA induction of bcl-Xs and bax genes and the internucleosomal DNA lad ders by taxotere was significant, respectively (p,0.05). The induction of b cl-Xs gene into MKN45 gastric cancer cells increased the sensitivity to VP- 16 and taxotere 2-3 fold in the IC50 values, whereas the induction of bax g ene increased the sensitivity to CDDP, VP-16, and taxotere 2-5 fold in the IC50 values, as compared to that of the Neo-transfected MKN45 cells. The mR NA overexpression of bax gene was found in the bcl-Xs-transfected cells. Li kewise, the mRNA overexpression of bcl-Xs gene was also found in the bax-tr ansfected cells. These results indicate that the activation of bcl-2 family genes such as bcl-Xs and bax plays a critical role in modulating apoptotic cell death in the sensitivity to anti-cancer drugs, and suggest that these proapoptotic genes might interact in the up-regulation for activating down stream signals leading to apoptosis in gastric cancer cells.