基础医学与临床 ›› 2016, Vol. 36 ›› Issue (5): 672-677.

• 研究论文 • 上一篇    下一篇

胃癌细胞中miR-135a表达对紫杉醇敏感性的影响

田甜甜,李艳艳,沈琳,高静   

  1. 北京肿瘤医院
  • 收稿日期:2016-01-15 修回日期:2016-03-16 出版日期:2016-05-05 发布日期:2016-04-26
  • 通讯作者: 高静 E-mail:gaojing_pumc@163.com
  • 基金资助:
    国家自然科学基金

Effect of miR-135a expression on the sensitivity of paclitaxel in gastric cancer cells

  • Received:2016-01-15 Revised:2016-03-16 Online:2016-05-05 Published:2016-04-26

摘要: 目的 研究胃癌细胞中miR-135a表达与紫杉醇敏感性的关系,并探索可能的作用机制。方法 运用Taqman microRNA芯片筛选接受紫杉醇化疗有效及无效胃癌患者血清中差异表达microRNAs,选择与紫杉醇敏感性关系较大的microRNA-135a (miR-135a)为研究对象,在体外培养的胃癌细胞中转染miR-135a mimic与miR-Ctrl,用细胞增殖曲线、流式细胞仪、Western blot等方法探索miR-135a表达对紫杉醇敏感性的影响及可能的作用机制。结果 miR-135a在紫杉醇化疗无效患者血清中的表达水平明显高于化疗有效患者(P<0.05),可能与紫杉醇耐药有关。miR-135a通过抑制紫杉醇诱导的细胞周期G2期阻滞及细胞凋亡(P<0.05)而降低胃癌细胞对紫杉醇的敏感性。 结论 miR-135a有望成为临床胃癌紫杉醇化疗疗效的预测标志物。

关键词: 胃癌, miR-135a, 紫杉醇, 耐药

Abstract: Objective To investigate the relationship between miR-135a expression and paclitaxel sensitivity in gastric cancer cells, and explore the possible mechanisms. Methods The differential microRNAs were screened using Taqman microRNA assay in the serum of gastric cancer patients with different efficacies treated with paclitaxel chemotherapy. microRNA-135a (miR-135a), which had relationship with paclitaxel sensitivity, was selected in the following study. The influence and possible mechanisms of miR-135a expression on the sensitivity of paclitaxel in gastric cancer cells were investigated by using cell proliferation curve, flow cytometry, and Western blot. Results The expression level of miR-135a in patients with progressive disease treated with paclitaxel was significantly higher than that in patients with partial response(P<0.05), suggesting its relationship with paclitaxel resistance. miR-135a could decrease the sensitivity of paclitaxel in gastric cancer cells through inhibiting cell cycle arrest at G2 phase and cell apoptosis induced by paclitaxel(P<0.05). Conclusions miR-135a might be a predictive marker for paclitaxel efficacy in future clinical practice.

Key words: gastric cancer, miR-135a, paclitaxel, resistance