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 cancers 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. Pre-treatment of cancer cells with oxaliplatin significantly increased the radiosensitivity through induction of apoptosis by potently inhibiting survivin.
Khan
Zakir
Z
Department of Biotechnology, Madhav Institute of Technology and Science, Gwalior, India. khanzq@gmail.com
Khan
Noor
N
Tiwari
Ram P
RP
Patro
Ishan K
IK
Prasad
G B K S
GB
Bisen
Prakash S
PS
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D011836:Radiation Tolerance; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D015853:Cysteine Proteinase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009944:Organoplatinum Compounds; D000077022:Survivin; D000077150:Oxaliplatin