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.
Lee
Dae-Yeol
DY
Department of Pediatrics and Research Institute of Clinical Medicine, Chonbuk National University Medical School, 634-18, Keumam-dong, Jeonju, Jeonbuk 561-712, South Korea. leedy@moak.chonbuk.ac.kr
Yi
Ho Keun
HK
Hwang
Pyoung Han
PH
Oh
Youngman
Y
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000235:genetics
D000970:Antineoplastic Agents; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D005047:Etoposide; D017239:Paclitaxel