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miR-383-5p恢复与紫杉醇联合治疗MDA-MB-231乳腺癌

The combined therapy of miR-383-5p restoration and paclitaxel for treating MDA-MB-231 breast cancer.

作者信息

Dastmalchi Narges, Azarbarzin Shirin, Safaralizadeh Reza, Khojasteh Seyed Mahdi Banan, Shadbad Mahdi Abdoli, Amini Mohammad, Baghbanzadeh Amir, Asl Elmira Roshani, Baghbani Elham, Lotfinejad Parisa, Baradaran Behzad

机构信息

Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, 5166616471, Tabriz, Iran.

Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Med Oncol. 2021 Nov 10;39(1):9. doi: 10.1007/s12032-021-01606-7.

Abstract

The deregulation of microRNAs (miRs) has been identified in tumor development. Indeed, the restoration of tumor-suppressive miRs has been associated with inhibited tumor development in various cancers. Herein, we aimed to evaluate the impact of combined miR-383-5p restoration, as a tumor-suppressive miR, with taxol therapy in suppressing MDA-MB-231 breast cancer development. MDA-MB-231 cell line was restored with miR-383-5p and treated with paclitaxel both in combined and separate manners. The MTT experiment was carried out to measure the cytotoxicity of the therapeutic approaches on the tumoral cells. Besides, flow cytometry was conducted to assess apoptosis and cell cycle status following the treatments. Furthermore, the expression levels of critical factors contributed to tumor proliferation, migration, apoptosis were investigated via the qRT-PCR and western blotting techniques. The outcomes pointed out that the miR-383-5p might substantially enhance the chemosensitivity of MDA-MB-231 to taxol. Besides, miR-383-5p restoration and the combined therapy of miR-383-5p restoration with paclitaxel could remarkably increase apoptosis, decrease cell viability, arrest the cell cycle, inhibit clonogenicity, suppress tumor migration, suppress the PI3K/Akt signaling pathway, and down-regulate PD-L1 expression of BC cells. The restoration of miR-383-5p can enhance the chemosensitivity of MDA-MB-231 cells to taxol. Despite the anti-tumoral effects of miR-383-5p restoration on MDA-MB-231 breast cancer development, the combined therapy of miR-383-5p restoration with paclitaxel can be more effective in repressing MDA-MB-231 breast cancer development.

摘要

微小RNA(miR)失调已在肿瘤发展过程中被发现。事实上,肿瘤抑制性miR的恢复与多种癌症中肿瘤发展受抑制有关。在此,我们旨在评估作为肿瘤抑制性miR的miR - 383 - 5p恢复联合紫杉醇治疗对抑制MDA - MB - 231乳腺癌发展的影响。用miR - 383 - 5p恢复MDA - MB - 231细胞系,并分别或联合使用紫杉醇进行处理。进行MTT实验以测量这些治疗方法对肿瘤细胞的细胞毒性。此外,采用流式细胞术评估处理后的细胞凋亡和细胞周期状态。此外,通过qRT - PCR和蛋白质印迹技术研究了促成肿瘤增殖、迁移、凋亡的关键因子的表达水平。结果指出,miR - 383 - 5p可能显著增强MDA - MB - 231对紫杉醇的化学敏感性。此外,miR - 383 - 5p恢复以及miR - 383 - 5p恢复与紫杉醇的联合治疗可显著增加细胞凋亡、降低细胞活力、使细胞周期停滞、抑制克隆形成、抑制肿瘤迁移、抑制PI3K/Akt信号通路,并下调乳腺癌细胞的PD - L1表达。miR - 383 - 5p的恢复可增强MDA - MB - 231细胞对紫杉醇的化学敏感性。尽管miR - 383 - 5p恢复对MDA - MB - 231乳腺癌发展具有抗肿瘤作用,但miR - 383 - 5p恢复与紫杉醇的联合治疗在抑制MDA - MB - 231乳腺癌发展方面可能更有效。

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