Atorvastatin inhibits glioma glycolysis and immune escape by modulating the miR-125a-5p/TXLNA axis.

IF 2.7 3区 生物学
Kang Gao, Tao Zhou, YingChun Yin, XiaoJie Sun, HePing Jiang, TangYue Li
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引用次数: 0

Abstract

Background: Conventional treatments, including surgery, radiotherapy and chemotherapy, have many limitations in the prognosis of glioma patients. Atorvastatin (ATOR) has a significant inhibitory effect on glioma malignancy. Thus, ATOR may play a key role in the search for new drugs for the effective treatment of gliomas.

Methods: U87 cells were treated with different doses of ATOR and transfected. Viability was assessed using MTT, proliferative ability was determined using the colony formation test, Bax and Bcl-2 were identified using Western blot, apoptosis was identified using flow cytometry, and U87 cell migration and invasion were detected using the Transwell assay. Glucose uptake, lactate secretion, and ATP production in U87 cell culture medium were quantified. The positive rates of IFN-γ and TNF-α in CD8T were measured through flow cytometry. Subcutaneous injection of U87 cells was carried out to construct an in vivo mouse model of gliom, followed by HE staining to assess the effects of ATOR and miR-125a-5p on tumor development.

Results: ATOR blocked the viability, proliferation, migration, and invasion of U87 cells through the miR-125a-5p/TXLNA axis, and suppressed glycolysis and immune escape of glioma cells. Furthermore, overexpressing miR-125a-5p enhanced the anti-tumor effect of ATOR in vivo.

Conclusion: ATOR blocks glioma progression by modulating the miR-125a-5p/TXLNA axis, further demonstrating that ATOR provides an effective therapeutic target for the treatment of glioma.

阿托伐他汀通过调节miR-125a-5p/TXLNA轴抑制胶质瘤糖酵解和免疫逃逸。
背景:传统的胶质瘤治疗方法包括手术、放疗和化疗,在胶质瘤患者的预后方面存在许多局限性。阿托伐他汀(ATOR)对胶质瘤恶性肿瘤有显著的抑制作用。因此,ATOR可能在寻找有效治疗胶质瘤的新药中发挥关键作用。方法:用不同剂量的ATOR处理U87细胞并转染。MTT法检测细胞活力,菌落形成法检测细胞增殖能力,Western blot法检测Bax和Bcl-2,流式细胞术检测细胞凋亡,Transwell法检测U87细胞迁移和侵袭。对U87细胞培养基中葡萄糖摄取、乳酸分泌和ATP产生进行了定量分析。流式细胞术检测CD8T中IFN-γ和TNF-α的阳性率。皮下注射U87细胞构建小鼠体内胶质瘤模型,HE染色评估ATOR和miR-125a-5p对肿瘤发展的影响。结果:ATOR通过miR-125a-5p/TXLNA轴阻断U87细胞的活力、增殖、迁移和侵袭,抑制胶质瘤细胞的糖酵解和免疫逃逸。此外,过表达miR-125a-5p可增强ATOR在体内的抗肿瘤作用。结论:ATOR通过调节miR-125a-5p/TXLNA轴阻断胶质瘤的进展,进一步证明ATOR为胶质瘤的治疗提供了一个有效的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Hereditas
Hereditas Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.80
自引率
3.70%
发文量
0
期刊介绍: For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.
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