Short hairpin RNA targeting c-FLIP sensitizes human cervical adenocarcinoma Hela cells to chemotherapy and radiotherapy
Short hairpin RNA targeting c-FLIP sensitizes human cervical adenocarcinoma Hela cells to chemotherapy and radiotherapy
复制标题
靶向 c-FLIP 的短发夹 RNA 使人宫颈腺癌细胞 Hela 细胞对化疗和放疗敏感。
DOI：
10.1016/j.canlet.2008.06.026
复制
发表时间：
2008-11-28
期刊：
影响因子：
9.7
通讯作者：
Ma, Ding
中科院分区：
文献类型：
--
作者：
Luo, Aiyue;Wang, Wei;Ma, Ding
c-FLIP 抑制死亡受体介导的 caspase-8 激活和细胞凋亡。本研究旨在确定基于 c-FLIP 靶向载体的短发夹 RNA (shRNA) 对细胞生长的影响，并评估其对宫颈腺癌 Hela 细胞对药物和放疗反应性的调节。 72小时后，转染针对c-FLIP的shRNA的细胞的cFLIP表达显着下调。 c-FLIP 沉默显着抑制细胞增殖并增加细胞凋亡。随着转染后时间的推移，用靶向cFLIP的shRNA诱导caspase-8和caspase-3的激活。此外，基于载体的针对 c-FLIP 的 shRNA 随后使 Hela 细胞对顺铂、iritican 和 Co60 放射治疗的敏感性增加了约 4 至 6 倍。我们的数据表明，基于载体的shRNA有效抑制c-FLIP表达，增强caspase-8和caspase-3的表达水平以诱导细胞凋亡，可能与常规化疗和放疗联合治疗宫颈腺癌具有更高的疗效。 (c) 2008 Elsevier Ireland Ltd. 保留所有权利。
c-FLIP inhibits caspase-8 activation and cell apoptosis mediated by death receptors. The present study aims at determining the effects of c-FLIP targeted vector-based short hairpin RNA (shRNA) on cell growth and evaluating its modulation of responsiveness to drugs and radiotherapy in cervical adenocarcinoma Hela cells. cFLIP expression of the cells transfected with shRNA against c-FLIP was significantly down-regulated after 72 h. c-FLIP silencing markedly suppressed cell proliferation and increased cell apoptosis. The activation of caspase-8 and caspase-3 was induced with shRNA targeting cFLIP with the passage of time after transfection. Furthermore, Vector-based shRNA against c-FLIP subsequently increased the sensitivity to cisplatin, iritican and Co60 radiotherapy by about 4- to 6-folds in Hela cells. Our data suggest that vector-based shRNA effectively inhibited c-FLIP expression, enhanced the expression level of caspase-8 and caspase-3 to induce cell apoptosis, probably with the higher efficacy in combination therapies with conventional chemotherapy and radiotherapy in cervical adenocarcinoma. (c) 2008 Elsevier Ireland Ltd. All rights reserved.