Down-regulation of survivin by oxaliplatin diminishes radioresistance of head and neck squamous carcinoma cells

Background Oxaliplatin is integrated in treatment strategies against a variety of cancels including radiation protocols Herein, as a new strategy we tested feasibility and rationale of oxaliplatin in combination with radiation to control proliferation of head and neck squamous cell carcinoma (HNSCC) cells and discussed survivin-related signaling and apoptosis induction. Methods Cytotoxicity and apoptosis induced by radiation and/or oxaliplatin were examined in relation to survivin status using two HNSCC cell lines viz, Cal27 and NT8e, and one normal 293-cell line Survivin gene knockdown by siRNA was also tested in relevance to oxaliplatin-mediated radiosensitization effects Results Survivin plays a critical role in mediating radiation-resistance in part through suppression of apoptosis via a caspase-dependent mechanism. Oxaliplatin treatment significantly decreased expression of survivin in cancer cells within 24-72 h. Apoptotic cells and caspase-3 activity were increased parallely with decrease in cell viability, if irradiated during this sensitive period The cytotoxicity of oxaliplatin and radiation combination was greater than additive Survivin gene knockdown experiments have demonstrated the role of survivin in radiosensitization of cancer cells mediated by oxaliplatin Conclusions Higher expression of survivin is a critical factor for radioresistance in HNSCC cell lines Pretreatment of cancer cells with oxaliplatin significantly increased the radiosensitivity through induction of apoptosis by potently inhibiting survivin (C) 2010 Elsevier Ireland Ltd All rights reserved Radiotherapy and Oncology 96 (2010) 267-273