Enhanced expression of insulin-like growth factor binding protein-3 sensitizes the growth inhibitory effect of anticancer drugs in gastric cancer cells.

Insulin-like growth factor (IGF)-I and -II are potent mitogens and their mitogenic effects are modulated by IGF binding proteins (IGFBPs). In this study, we evaluated whether the enhanced expression of IGFBP-3 may increase the sensitivity of human gastric cancer cells to the anticancer drugs. We further investigated the potential mechanism for the growth inhibitory effect of anticancer drug induced-IGFBP-3 expression. These IGFBP-3-expressing gastric cancer cells showed a lower proliferation rate than IGFBP-3-non-expressing cells. Treatment with anticancer drugs resulted in up-regulation of IGFBP-3 expression in IGFBP-3-expressing cells. Interestingly the anticancer drug-induced-growth inhibition was more evident in IGFBP-3-expressing cells causing the IGFBP-3 expressing cells but not the IGFBP-3 non-expressing cells to accumulate in the G1/G0 phase and induce apoptosis. The exogenous addition of IGFBP-3 inhibited the growth of IGFBP-3-non-expressing cells, causing them to undergo apoptosis. Our data suggest that IGFBP-3 may have an important role in the biology of gastric cancer cell growth and provides a potential marker for predicting the responsiveness to anticancer drugs. (c) 2002 Elsevier Science (USA).