Department of Oral & Maxillofacial Surgery, Guanghua School of Stomatology & Hospital of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
Oncol Res. 2010;18(8):377-85. doi: 10.3727/096504010x12644422320663.
Survivin is a member of the inhibitor of apoptosis protein (IAP) family; it is overexpressed in most cancer tissues and induces resistance to chemotherapy. In this study, we investigated whether a short hairpin RNA (shRNA) targeting survivin can induce apoptosis and enhance chemosensitivity to cisplatin in squamous cell carcinoma of the tongue. Results showed that chemosensitivity to cisplatin was surviving dependent in three cell lines (Tca8113, Bca885, and MCF7); higher survivin mRNA expression levels were associated with lower sensitivity to cisplatin. A plasmid-containing survivin shRNA was constructed and transfected into cell line Tca8113. Survivin shRNA inhibited expression of survivin mRNA and protein (63% and 65% inhibition, respectively), significantly inhibited cell proliferation, and enhanced chemosensitivity to cisplatin (p < 0.05). Apoptosis and caspase-3 activity were induced when cells were treated with survivin shRNA and/or cisplatin. Survivin shRNA induced caspase-3-dependent apoptosis and enhanced chemosensitivity to cisplatin in these tongue squamous cell carcinoma cell lines.
Survivin 是凋亡抑制蛋白(IAP)家族的一员;它在大多数癌症组织中过度表达,并诱导对化疗的耐药性。在这项研究中,我们研究了靶向 survivin 的短发夹 RNA(shRNA)是否可以诱导舌鳞状细胞癌细胞的凋亡并增强顺铂的化疗敏感性。结果表明,三种细胞系(Tca8113、Bca885 和 MCF7)中顺铂的化疗敏感性依赖于 survivin;survivin mRNA 表达水平越高,对顺铂的敏感性越低。构建了含有 survivin shRNA 的质粒并转染至细胞系 Tca8113。Survivin shRNA 抑制 survivin mRNA 和蛋白的表达(分别抑制 63%和 65%),显著抑制细胞增殖,并增强顺铂的化疗敏感性(p<0.05)。当用 survivin shRNA 和/或顺铂处理细胞时,诱导细胞凋亡和 caspase-3 活性。Survivin shRNA 在这些舌鳞状细胞癌细胞系中诱导 caspase-3 依赖性凋亡并增强顺铂的化疗敏感性。