Suppr超能文献

微小RNA-30通过调节细胞自噬降低人胃癌细胞的多药耐药性。

miR-30 decreases multidrug resistance in human gastric cancer cells by modulating cell autophagy.

作者信息

Du Xinming, Liu Bing, Luan Xuerong, Cui Qing, Li Leping

机构信息

Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.

Department of Gastrointestinal Surgery, Zibo Central Hospital, Zibo, Shandong 250020, P.R. China.

出版信息

Exp Ther Med. 2018 Jan;15(1):599-605. doi: 10.3892/etm.2017.5354. Epub 2017 Oct 23.

Abstract

Chemotherapy is an important treatment modality for gastric cancer, and multidrug resistance (MDR) represents a major obstacle for successful cancer chemotherapy. There is a lack of research on whether microRNA (miR)-30a regulation affects the chemosensitivity of resistant gastric cancer cells, and mechanisms underlying the effects of miR-30a on drug resistance and cell autophagy require further investigation. In the present study, the expression of miR-30a and its effects in cisplatin (CDDP)-resistant human gastric cancer cells were investigated. A CDDP-resistant variant of the SGC-7901 cell line (SGC-7901/CDDP) was established by exposing the cells to gradually increasing drug concentrations, and miR-30a expression was detected by reverse transcription-semi quantitative polymerase chain reaction (RT-sqPCR). To examine the effect of miR-30a expression in the SGC-7901/CDDP cells, miR30a mimics or negative control miRNA were transfected into the cells, and a Cell Counting Kit-8 assay was performed to analyze the chemosensitivity of the different cell groups. RT-sqPCR and western blot analysis were also used to measure mRNA and P-glycoprotein expression, and the light chain (LC)3-II/LC3-I ratio. Furthermore, apoptosis induced by the chemotherapeutic CDDP in the different groups was assessed using flow cytometry. The results demonstrated that low expression of miR-30a was associated with chemoresistance in gastric cancer cells, and in the chemoresistant cell line SGC7901/CDDP, CDDP-induced apoptosis was weakened. Additionally, it was demonstrated that the LC3-II/LC3-I ratio was elevated in SGC7901/CDDP cells compared with chemosensitive SGC7901 cells (P<0.001), which could be attenuated by upregulating miR-30a expression (P<0.001 vs. SGC7901/CDDP control cells). These results suggested that autophagy may contribute to drug resistance in gastric cancer cells, and that the reduction of LC3-II in response to miR-30a overexpression may inhibit chemoresistance-associated autophagy in gastric cancer cells.

摘要

化疗是胃癌的一种重要治疗方式,而多药耐药(MDR)是癌症化疗成功的主要障碍。关于微小RNA(miR)-30a调控是否影响耐药胃癌细胞的化疗敏感性,目前缺乏相关研究,miR-30a对耐药性和细胞自噬影响的机制尚需进一步研究。在本研究中,对miR-30a在顺铂(CDDP)耐药的人胃癌细胞中的表达及其作用进行了研究。通过将SGC-7901细胞系暴露于逐渐增加的药物浓度中,建立了一种CDDP耐药变体(SGC-7901/CDDP),并通过逆转录-半定量聚合酶链反应(RT-sqPCR)检测miR-30a的表达。为了检测miR-30a在SGC-7901/CDDP细胞中的表达效果,将miR-30a模拟物或阴性对照miRNA转染到细胞中,并用细胞计数试剂盒-8检测法分析不同细胞组的化疗敏感性。还使用RT-sqPCR和蛋白质印迹分析来检测mRNA和P-糖蛋白的表达,以及轻链(LC)3-II/LC3-I的比值。此外,使用流式细胞术评估不同组中化疗药物CDDP诱导的细胞凋亡。结果表明,miR-30a的低表达与胃癌细胞的化疗耐药相关,在化疗耐药细胞系SGC7901/CDDP中,CDDP诱导的细胞凋亡减弱。此外,结果表明,与化疗敏感的SGC7901细胞相比,SGC7901/CDDP细胞中LC3-II/LC3-I的比值升高(P<0.001),而上调miR-30a的表达可使其降低(与SGC7901/CDDP对照细胞相比,P<0.001)。这些结果表明,自噬可能导致胃癌细胞的耐药,并且miR-30a过表达导致的LC3-II减少可能抑制胃癌细胞中与化疗耐药相关的自噬。

相似文献

引用本文的文献

5
Mechanism of cisplatin resistance in gastric cancer and associated microRNAs.胃癌顺铂耐药的机制及相关 microRNAs。
Cancer Chemother Pharmacol. 2023 Nov;92(5):329-340. doi: 10.1007/s00280-023-04572-1. Epub 2023 Aug 3.
9
Regulation of autophagy by non-coding RNAs in gastric cancer.非编码RNA对胃癌自噬的调控
Front Oncol. 2022 Oct 24;12:947332. doi: 10.3389/fonc.2022.947332. eCollection 2022.

本文引用的文献

2
Regulation of multidrug resistance by microRNAs in anti-cancer therapy.微小RNA在抗癌治疗中对多药耐药性的调控
Acta Pharm Sin B. 2017 Jan;7(1):38-51. doi: 10.1016/j.apsb.2016.09.002. Epub 2016 Dec 3.
5
Molecular mechanisms of chemoresistance in gastric cancer.胃癌化疗耐药的分子机制
World J Gastrointest Oncol. 2016 Sep 15;8(9):673-81. doi: 10.4251/wjgo.v8.i9.673.
6
Noncoding RNAs in gastric cancer: Research progress and prospects.胃癌中的非编码RNA:研究进展与展望
World J Gastroenterol. 2016 Aug 7;22(29):6610-8. doi: 10.3748/wjg.v22.i29.6610.
7
Functional role of autophagy in gastric cancer.自噬在胃癌中的功能作用。
Oncotarget. 2016 Apr 5;7(14):17641-51. doi: 10.18632/oncotarget.7508.
9
Molecular targeted therapy for the treatment of gastric cancer.用于治疗胃癌的分子靶向治疗
J Exp Clin Cancer Res. 2016 Jan 4;35:1. doi: 10.1186/s13046-015-0276-9.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验