shRNA Depletion of cIAPl Sensitizes Human Ovarian Cancer Cells to Anticancer Agent-Induced Apoptosis

摘要

Emerging evidence suggests a potential role of cellular inhibitor of apoptosis protein 1 (cIAPl) in the development of human ovarian cancer. However, its function in the progression of ovarian cancer has not been clearly determined. Our study aimed to investigate the effect of cIAPl gene depletion on the chemosensitiv-ity of ovarian cancer cells. We developed a novel short hairpin RNA (shRNA) plasmid specifically targeting cIAPl. Cell proliferation, invasion, and apoptosis of the shRNA-transfected cells were evaluated using MTT, Transwell chamber, and flow cytometric assays, respectively. The concentration of MMP-9 in the supernatant was detected by ELISA. Targeted depletion of cIAPl by shRNA significantly reduced expression levels of cIAPl mRNA and protein, leading to inhibition of cell proliferation and invasion capability in SKOV3 cells. At the same time, cIAPl downregulation decreased the secretion of MMP-9. shRNA depletion of cIAPl enhanced chemosensitivity of ovarian cancer cells to Taxol and carboplatin-induced apoptosis. cIAPl is associated with tumor progression in human ovarian cancer. Therefore, cIAPl might be a potential target for therapeutic anticancer drugs.