Knockdown of survivin contributes to antitumor activity in cisplatin-resistant ovarian cancer cells.

Abstract

Survivin (SVV) is an important member of the inhibitor of apoptosis family. It is overexpressed in a number of cancer types, including human ovarian carcinomas. SVV promotes invasion, metastasis, growth and survival of malignant cells and confers resistance to specific chemotherapeutic drugs. The present study aimed to elucidate the role and possible mechanisms of SVV in cisplatin-resistant ovarian cancer cells (A2780/CP). Using a loss-of-function approach, we investigated the effects of adenovirus-mediated knockdown of SVV by small hairpin RNA (ad5-SVV) on the expression of pro-caspase-3, cleaved caspase-3, proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2 (MMP-2) in A2780/CP cells by real-time PCR and western blot analysis. Proliferation was measured by MTT assay, invasive potential by Transwell, and cell apoptosis by FITC-Annexin V and propidium iodide for the functional analysis of A2780/CP cells following infection with ad5-SVV. As a result, knockdown of SVV downregulated the expression of PCNA and MMP-2 and upregulated the expression of pro-caspase-3 and cleaved caspase-3. In addition, knockdown of SVV enhanced cisplatin-induced proliferative activities, induced cell apoptosis and inhibited the invasive potential in A2780/CP cells. The present findings demonstrate that knockdown of SVV contributes to antitumor activity in cisplatin-resistant ovarian cancer cells via the downregulation of PCNA and MMP-2 expression and the upregulation of caspase-3 expression and indicate that SVV is a potential target for therapeutic anticancer drugs.