南方医科大学学报

南方医科大学学报 ›› 2022, Vol. 42 ›› Issue (6): 899-904.doi: 10.12122/j.issn.1673-4254.2022.06.14

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阿托伐他汀抑制脑胶质瘤细胞的增殖和促进凋亡：基于上调miR-146a表达与抑制PI3K/Akt信号通路

崔 颖，范顺志，潘迪迪，巢 青   

  1. 蚌埠医学院第二附属医院神经外科，安徽 蚌埠 233000
  • 出版日期:2022-06-20 发布日期:2022-06-27

Atorvastatin inhibits malignant behaviors and induces apoptosis in human glioma cells by up-regulating miR-146a and inhibiting the PI3K/Akt signaling pathway

CUI Ying, FAN Shuizhi, PAN Didi, CHAO Qing   

  1. Department of Neurosurgery, Second Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
  • Online:2022-06-20 Published:2022-06-27

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摘要： 目的 探究阿托伐他汀（AVT）对人脑胶质瘤细胞生物学行为的影响及其对miR-146a/PI3K/Akt信号通路的作用。方法 将人脑胶质瘤细胞U251分为4组：对照组（Conrtrol）、AVT组、AVT+转染miR-146a无关片段组（AVT+miR-146a NC）、AVT+转染miR-146a干扰组（AVT+miR-146a inhibitor）。Control组不加任何药物，AVT组加入8.0 μmol/L 的AVT，AVT+miR-146a NC组转染miR-146a NC后加入8.0 μmol/L 的AVT，AVT+miR-146a inhibitor组转染miR-146a inhibitor后加入8.0 μmol/L 的AVT。RT-PCR检测miR-146a表达，MTT检测细胞增殖率，流式细胞术检测细胞凋亡情况，Transwell实验检测细胞侵袭和迁移情况，Western blot检测PI3K/Akt信号通路相关蛋白表达。结果 药物干预48 h，与Control组相比，AVT组细胞miR-146a表达、细胞凋亡率均明显升高（P<0.01），细胞增殖率、侵袭指数、迁移指数、p-PI3K和p-Akt蛋白表达均明显降低（P<0.01）。与AVT组相比，AVT+miR-146a inhibitor组细胞miR-146a表达、细胞凋亡率均明显降低（P<0.01），细胞增殖率、侵袭指数、迁移指数、p-PI3K 和p-Akt蛋白表达均明显升高（P<0.01），AVT+miR-146a NC组上述指标无显著性差异（P>0.05）。结论 AVT能够抑制人脑胶质瘤细胞增殖、侵袭和迁移，促进细胞凋亡，其机制与上调miR-146a表达，抑制PI3K/Akt信号通路相关。

关键词: 人脑胶质瘤；U251；阿托伐他汀；miR-146a；PI3K/Akt；生物学行为

Abstract: Objective To explore the effect of atorvastatin (AVT) on biological behaviors and the miR-146a/PI3K/Akt signaling pathway in human glioma cells. Methods Human glioma U251 cells were treated with 8.0 μmol/L AVT or transfected with a miR-146a inhibitor or a negative control fragment (miR-146a NC) prior to AVT treatment. RT-PCR was used to detect miR-146a expression in the cells, and the changes in cell proliferation rate, apoptosis, cell invasion and migration were detected using MTT assay, flow cytometry, and Transwell assay. Western blotting was performed to detect the changes in cellular expressions of proteins in the PI3K/Akt signaling pathway. Results AVT treatment for 48 h resulted in significantly increased miR-146a expression and cell apoptosis (P<0.01) and obviously lowered the cell proliferation rate, invasion index, migration index, and expressions of p-PI3K and p-Akt protein in U251 cells (P<0.01). Compared with AVT treatment alone, transfection with miR-146a inhibitor prior to AVT treatment significantly reduced miR-146a expression and cell apoptosis (P<0.01), increased the cell proliferation rate, promoted cell invasion and migration, and enhanced the expressions of p-PI3K and p-Akt proteins in the cells (P<0.01); these effects were not observed following transfection with miR-146a NC group (P>0.05). Conclusion AVT can inhibit the proliferation, invasion and migration and promote apoptosis of human glioma cells possibly by up-regulating miR-146a expression and inhibiting the PI3K/Akt signaling pathway.

Key words: human glioma; U251 cells; atorvastatin; miR-146a; PI3K/Akt; biological behaviors