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中国癌症防治杂志 ›› 2021, Vol. 13 ›› Issue (3): 231-236.doi: 10.3969/j.issn.1674-5671.2021.03.01

• 基础研究 •    下一篇

白藜芦醇对人胃癌耐药细胞SGC-7901/5-FU生物学效应的影响及其作用机制

  

  1. 上海中医药大学附属曙光医院急诊科
  • 出版日期:2021-06-25 发布日期:2021-07-07
  • 通讯作者: 何淼, E-mail:13671503856@126.com
  • 基金资助:
    上海市临床重点专科项目(shslczdzk04402)

Effect of resveratrol on biological effects of human gastric cancer SGC-7901/5-FU cells and its mechanisms

  • Online:2021-06-25 Published:2021-07-07

摘要: 目的 探讨白藜芦醇(resveratrol,RES)对5-氟尿嘧啶(5-fluorouracil,5-FU)耐药胃癌细胞(SGC-7901/5-FU)生物学效应的影响及其作用机制。方法 用不同浓度(0 μmol/L、10 μmol/L、50 μmol/L、200 μmol/L、400 μmol/L)的RES分别处理SGC-7901/5-FU细胞24 h、48 h与72 h,其次用100 μmol/L浓度的RES与5-FU(5 μmol/L)单独或联合处理SGC-7901/5-FU细胞48 h。CCK-8法检测细胞增殖情况,流式细胞术检测细胞凋亡情况,免疫荧光染色法观察细胞形态。RT-PCR检测多药耐药基因MDR1以及凋亡相关基因Bcl2与Caspase 3的mRNA表达水平,Western blot检测P-gp、Bcl2和Caspase 3蛋白的表达水平。 结果 不同浓度RES均能抑制SGC-7901/5-FU细胞增殖,且具有时间与剂量依赖效应;RES组、5-FU组及联合组均能诱导SGC-7901/5-FU细胞凋亡,细胞出现凋亡样形态改变,其中联合组变化最明显(P<0.001);RES组和联合组中MDR1 mRNA与P-gp蛋白表达水平均下降(P<0.05),且联合组变化更明显;RES组、5-FU组及联合组中Bcl2 mRNA与蛋白表达水平均下降(P<0.001),Caspase 3 mRNA与蛋白表达水平均上升(P<0.001),其中联合组变化最明显。结论 RES通过下调多药耐药基因MDR1/P-gp蛋白表达抑制胃癌耐药细胞SGC-7901/5-FU细胞增殖并诱导细胞凋亡,降低细胞耐药性。

关键词: 胃癌, 白藜芦醇, 耐药性, 细胞凋亡

Abstract: Objective  To investigate the effect of resveratrol (RES) on the biological effects of SGC-7901/5-FU cells and its mechanisms. Methods The SGC-7901/5-FU cells were treated with RES at concentrations of 0 μmol/L, 10 μmol/L, 50 μmol/L, 200 μmol/L and 400 μmol/L, respectively, for 24 h, 48 h and 72 h, and then SGC-7901/5-FU cells were treated, with RES (100 μmol/L) and 5-FU (5 μmol/L), respectively or simultaneously, for 48 h. The cell proliferation was detected by CCK-8 method, the apoptosis by flow cytometry, and the cell morphology by immunofluorescence staining method. The mRNA expression levels of MDR1, Bcl2 and Caspase 3 were detected by RT-PCR, and the protein expression levels of P-gp, Bcl2 and caspase 3 were detected by Western blot. Results RES with different concentrations could inhibit the proliferation of SGC-7901/5-FU cells effectively, depending upon time and dose. The RES group, 5-FU group and combined group could induce apoptotic and morphology changes in SGC-7901/5-FU cells, which was most remarkable in the combined group(P<0.001). The expression levels of MDR1 mRNA and P-gp protein in RES group and combined group were decreased (P<0.05), which was more significant in combined group; the Bcl2 mRNA and protein expression levels were decreased in RES group, 5-FU group and combined group (P<0.001), while Caspase 3 mRNA and protein expression levels were increased (P<0.001), which was more pronounced in the combined group. Conclusions RES can inhibit the proliferation of SGC-7901/5-FU cells by down-regulating the expression of drug-resistance related gene MDR1/P-gp protein and induce cell apoptosis to reduce drug resistance.

Key words: Gastric cancer, Resveratrol, Drug resistance, Apoptosis

中图分类号: 

  • R735.2