临床肿瘤学杂志 ›› 2018, Vol. 23 ›› Issue (9): 790-794.

• 论著 • 上一篇    下一篇

白藜芦醇逆转胃癌细胞对阿帕替尼耐药性的实验研究

  

  1. 430060  武汉  武汉大学人民医院肿瘤中心Ⅱ科

  • 收稿日期:2018-07-03 修回日期:2018-08-07 出版日期:2018-09-30 发布日期:2018-11-28
  • 通讯作者: 戈 伟 E-mail:lijun2334@163.com

Experimental study of resveratrol reverses the resistance of gastric cancer cells to apatinib

  1. Department of Ⅱ, Cancer Center, People’s Hospital of Wuhan University, Wuhan 430060, China

  • Received:2018-07-03 Revised:2018-08-07 Online:2018-09-30 Published:2018-11-28
  • Contact: GE Wei E-mail:lijun2334@163.com

摘要: 目的 探讨白藜芦醇(RES)在胃癌细胞对阿帕替尼耐药性中的影响及可能机制。方法 体外培养胃癌SGC7901细胞和SGC7901/AR耐药细胞,MTT法和划痕实验检测单药不同浓度阿帕替尼或联合RES对SGC7901和SGC7901/AR细胞增殖和迁移的影响,分别计算SGC7901和SGC7901/AR细胞耐药指数、RES的逆转倍数(RF)和相对逆转率(RRR)。采用实时荧光定量PCR(QPCR)检测上述处理细胞株中miR-122、p-VEGFR2、p-Akt mRNA表达。结果 阿帕替尼显著抑制SGC7901细胞的增殖和迁移能力,并呈浓度依赖性(P<0.05),但对SGC7901/AR细胞无影响,耐药指数为15.57;阿帕替尼联合50.0 μmol/L RES可显著抑制SGC7901和SGC7901/AR细胞的增殖和迁移能力,并呈浓度依赖性(P<0.05),耐药指数为2.13,RES的逆转倍数为7.91倍,相对逆转率为93.4%。未经处理SGC7901细胞中miR-122、p-VEGFR和p-Akt mRNA表达水平分别为0.74±0.11、0.76±0.13和0.67±0.09,显著高于SGC7901/AR细胞(P<0.05);经10 μmol/L阿帕替尼作用后,SGC7901细胞中p-VEGFR2和p-Akt mRNA表达水平显著下降(P<0.05)。经10 μmol/L阿帕替尼+50.0 μmol/L RES处理后,SGC7901和SGC7901/AR细胞中miR-122表达显著升高(P<0.05),而p-VEGFR2和p-AktmRNA表达水平显著降低(P<0.05)。结论 RES能逆转胃癌细胞株对阿帕替尼的耐药性,其机制可能通过上调miR-122并抑制VEGFR2和Akt磷酸化水平来实现。

关键词: 胃癌, 白藜芦醇, 微小核糖核酸, 阿帕替尼, 敏感性

Abstract: Objective To investigate the effect and possible mechanism of resveratrol (RES) on the resistance of gastric cancer cell to apatinib. Methods  SGC7901 and SGC7901/AR cells were cultured in vitro. MTT assay and scratch test were used to detect the effects of different concentrations of apatinib or combined with RES on proliferation and migration of SGC7901 and SGC7901/AR cells. Resistance index, reversal multiple (RF) and relative reversal rate (RRR) of SGC7901 and SGC7901/AR cells were calculated respectively. Real-time fluorescence quantitative PCR (QPCR) was used to detect the miR-122, p-VEGFR2, p-Akt mRNA in these cells. Results Apatinib significantly inhibited the proliferation and migration of SGC7901 cells in a concentration-dependent manner (P<0.05), and the resistance index was 15.57. Apatinib combined with 50.0 μmol/L RES significantly inhibited the proliferation and migration of SGC7901 and SGC7901/AR cells in a concentration-dependent manner (P<0.05). The resistance index was 2.13, the reversal ratio of RES was 7.91 times, and the relative reverse rate was 93.4%. The expression levels of miR-122, p-VEGFR2, p-Akt mRNA in untreated SGC7901 cells were 0.74±0.11, 0.76±0.13 and 0.67±0.09, respectively, which were significantly higher than those in SGC7901/AR cells (P<0.05). The expression levels of p-VEGF R2 and p-Akt mRNA in SGC7901 cells decreased significantly after treatment with 10 μmol/L apatinib (P<0.05). After treatment with 10 μmol/L apatinib and 50.0 μmol/L RES, the expression of miR-122 in SGC7901 and SGC7901/AR cells increased significantly (P<0.05), while the expression of p-VEGFR2 and p-Akt mRNA decreased significantly (P<0.05). Conclusion Resveratrol can reverse the drug resistance of gastric cancer cell lines to apatinib, possibly by up-regulating the level of miR-122 and inhibiting the phosphorylation of VEGFR2 and Akt.

Key words: Gastric cancer, Resveratrol, MicroRNAs, Aapatinib, Sensitivity

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