School of Studies in Biotechnology, Jiwaji University, Gwalior 474011, India.
Curr Gene Ther. 2012 Dec;12(6):444-53. doi: 10.2174/156652312803519805.
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.
存活素在各种癌中呈高表达，与它们的生物学侵袭性特征和耐药性有关。我们之前曾报道过存活素是一种重要的抗细胞凋亡蛋白，参与头颈部鳞状细胞癌（HNSCC）的肿瘤发生，并对常规癌症治疗产生耐药性。本研究的目的是探讨存活素作为 HNSCC 治疗靶点的潜力。本研究旨在探讨 survivin-siRNA 治疗对头颈部鳞状细胞癌细胞凋亡的影响及其对顺铂敏感性的影响。设计了慢病毒载体将 survivin 特异性 siRNA 递送到癌细胞中。数据表明，慢病毒-siRNA 治疗沉默 survivin 可有效抑制癌细胞增殖，并诱导 HNSCC 细胞中 caspase 依赖性凋亡。研究还表明，HNSCC 细胞对临床相关水平的顺铂药物治疗的反应受到限制。我们观察到 survivin 是这种顺铂耐药机制中的关键因素，下调 survivin 可显著增加癌细胞对顺铂诱导凋亡的敏感性。因此，这种联合治疗作为一种多模式治疗方案，具有显著改善头颈部癌症临床结局的潜力。
