Expression and role of the inhibitor of apoptosis protein livin in chemotherapy sensitivity of ovarian carcinoma

摘要

Ovarian cancer has the highest mortality rate of all gynecological malignancies. Livin, a novel member of the inhibitor of apoptosis protein family, has been found to be expressed in various malignancies and is suggested to have poor prognostic significance. However, no data are available concerning the significance of livin in ovarian cancer. In the present study, we detected the expression of livin isoforms in human epithelial ovarian cancer (EOC) tissues using semi-quantitative RT-PCR and western blot assays. The data indicated that livin expression positive ratio was much higher in cancer tissues compared to those in benign ovarian tumors and normal ovarian specimens. To determine the role of livin in the process of ovarian cancer growth, RNA interference mediated by recombinant lentivirus vectors expressing livin shRNA was applied to induce a long-lasting downregulation of livin gene expression in SKOV3 human ovarian cancer cell line. Cell apoptosis and chemosensitivity were evaluated by MTT assay and flow cytometry, respectively, following downregulation of livin expression, and the cleavage of molecular markers of the mitochondrial apoptotic signaling pathway was investigated by immunoblotting. Livin knockdown with siRNA enhanced spontaneous and drug-induced apoptosis in SKOV3 cells. The inhibition of livin resulted in profound pro-apoptotic and antiproliferative effects, and was associated with the activation of caspase signaling. In conclusion, these data suggested that livin plays an important role in inhibiting the apoptosis of ovarian cancer cells. Specific silencing of livin expression could promote cell apoptosis, enhance chemotherapy sensitivity and may be a promising target for further research in clinical chemotherapy of epitheliod ovarian cancer.