Induction of Apoptosis and Sensitization of Head and Neck Squamous Carcinoma Cells to Cisplatin by Targeting Survivin Gene Expression

Zakir      Khan; Ram      P. Tiwari; Noor      Khan; Godavarthi      B.K.S. Prasad; Prakash      S. Bisen

doi:10.2174/156652312803519805

Abstract

Survivin is known to be highly-expressed in various carcinomas; and is associated with their biologically aggressive characteristics and drug resistance. We have previously reported survivin as an important anti-apototic protein involved in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and providing resistance to conventional cancer therapies. The purpose of present study was to investigate the potential of survivin as a therapeutic target in HNSCC. This study was designed to explore the effect(s) of survivin-siRNA therapy on the apoptosis in HNSCC cells, and its influence on cisplatin-sensitivity. Lentivirus vector was developed to deliver survivin specific siRNA into cancer cells. The data indicates that silencing of survivin-mediated by Lentivirus-siRNA therapy effectively suppressed cancer cell proliferation and induced caspase-dependent apoptosis in HNSCC cells. The study also shows that the response of HNSCC cells to cisplatin drug treatment at clinically relevant level was limited. We observed survivin to be a key factor involved in this cisplatin-resistance mechanism, and down-regulation of survivin significantly increased sensitivity of cancer cells to cisplatin-mediated apoptosis. Thus, this combination therapy acts as a multimodality regimen with significant potential to improve clinical outcomes in head and neck cancers.

Keywords: Survivin, head and neck squamous cell carcinoma, lentivirus-siRNA therapy, cisplatin, Survivin, Head and Neck Squamous Cell Carcinoma, Lentivirus-siRNA Therapy, Cisplatin, Lentivirus vector , IAP, cancer progression, poor prognosis