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阿托伐他汀通过上调miR-146a并抑制PI3K/Akt信号通路来抑制人胶质瘤细胞的恶性行为并诱导其凋亡。

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

作者信息

Cui Y, Fan S, Pan D, Chao Q

机构信息

Department of Neurosurgery, Second Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2022 Jun 20;42(6):899-904. doi: 10.12122/j.issn.1673-4254.2022.06.14.

DOI:10.12122/j.issn.1673-4254.2022.06.14
PMID:35790441
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9257370/
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 ( < 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 ( < 0.01). Compared with AVT treatment alone, transfection with miR-146a inhibitor prior to AVT treatment significantly reduced miR-146a expression and cell apoptosis ( < 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 ( < 0.01); these effects were not observed following transfection with miR-146a NC group (>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.

摘要

目的

探讨阿托伐他汀(AVT)对人胶质瘤细胞生物学行为及miR-146a/PI3K/Akt信号通路的影响。

方法

将人胶质瘤U251细胞用8.0 μmol/L AVT处理,或在AVT处理前用miR-146a抑制剂或阴性对照片段(miR-146a NC)转染。采用RT-PCR检测细胞中miR-146a表达,并用MTT法、流式细胞术和Transwell法检测细胞增殖率、凋亡、细胞侵袭和迁移的变化。采用蛋白质印迹法检测PI3K/Akt信号通路中细胞蛋白表达的变化。

结果

AVT处理48 h后,U251细胞中miR-146a表达显著增加,细胞凋亡明显增加(<0.01),细胞增殖率、侵袭指数、迁移指数以及p-PI3K和p-Akt蛋白表达明显降低(<0.01)。与单独AVT处理相比,AVT处理前用miR-146a抑制剂转染可显著降低miR-146a表达和细胞凋亡(<0.01),增加细胞增殖率,促进细胞侵袭和迁移,并增强细胞中p-PI3K和p-Akt蛋白表达(<0.01);miR-146a NC组转染后未观察到这些效应(>0.05)。

结论

AVT可能通过上调miR-146a表达并抑制PI3K/Akt信号通路来抑制人胶质瘤细胞的增殖、侵袭和迁移并促进其凋亡。

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