| 孔 静,王 哲,杨云舒,吴 颖,凌 瑞.PRMT5调控三阴性乳腺癌对多西他赛敏感性的研究[J].,2018,(6):1050-1054 |
| PRMT5调控三阴性乳腺癌对多西他赛敏感性的研究 |
| Regulation of PRMT5 on the Sensitivity to Docetaxel of Triple Negative Breast Cancer |
| 投稿时间：2017-11-08 修订日期：2017-12-05 |
| DOI：10.13241/j.cnki.pmb.2018.06.010 |
| 中文关键词: 三阴性乳腺癌 蛋白质精氨酸甲基转移酶5 细胞周期 细胞凋亡 |
| 英文关键词: Triple-negative breast cancer PRMT5 Cell-cycle Apoptosis |
| 基金项目:国家自然科学基金项目（81572917） |
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| 中文摘要: |
| 摘要 目的：探讨蛋白质精氨酸甲基转移酶5(protein arginine methyltransferase 5，PRMT5)对三阴性乳腺癌对多西他赛敏感性的影响，为三阴性乳腺癌的治疗提供新的思路。方法：通过包装慢病毒构建PRMT5过表达稳转细胞系和PRMT5敲除细胞系。采用平板克隆测定不同浓度下多西他赛对于MDA-MB-231细胞和PRMT5过表达细胞增殖的影响。采用流式周期和凋亡检测不同浓度多西他赛对PRMT5过表达和PRMT5敲除以及MDA-MB-231亲本细胞的周期以及凋亡的影响。采用Western Blot方法检测PARP以及p21、p27及LC3等表达。结果：成功构建PRMT5过表达及敲除稳转系。与对应对照组(MDA-MB-231细胞)比较，4nM和8nM的多西他赛处理的PRMT5过表达细胞系(MDA-MB-231-PRMT5细胞)形成克隆率明显降低(P<0.05)，细胞凋亡率明显增加(P<0.05)，细胞周期p21分子表达增多(P<0.05)，但未随浓度增加增高(P<0.05)，cycling D1、PARP剪切体、LC3-Ⅱ的表达均明显增加(P<0.05)。4nM和8nM的多西他赛处理的PRMT5敲除稳转系(MDA-MB-231-shPRMT5)细胞凋亡率、p21、p27、cyclinD1、LC3-Ⅱ的表达均较对应对照组(MDA-MB-231细胞)明显降低(P<0.05)，LC3-Ⅱ表达水平较亲本低(P<0.05)。结论：PRMT5高表达可增加MDA-MB-231细胞对多西他赛的敏感性，PRMT5有望成为多西他赛临床治疗敏感性预测和方案选择的关键分子，并有望成为调控多西他赛等化疗药物耐药的新靶点。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the effect of protein arginine methyltransferase 5(PRMT5) on the sensitivity of triple negative breast cancer (TNBC) to Docetaxel and find a novel method to treat TNBC. Methods: The stable PRMT5-overexpression and PRMT5-konck down cells were obtained through packaging slow virus. The effect of different doses of docetaxel on the proliferation of MDA-MB-231-PRMT5 and MDA-MB-231 cells were detected by flat plate clone formation test. The cell cycle and apoptosis were detected by flow cytometry. The expression of PARP, p21, p27 and LC3-Ⅱ were examined by Western Blot. Results: The stable PRMT5-overexpression cells and PRMT5-knock down cells were successfully constructed. Compared to the MDA-MB-231 cell, the colony forming efficiency of MDA-MB-231-PRMT5 cells treated by 4nM and 8nM docetaxel were significantly lower(P<0.05), the apoptotic rates and p21, cycling D1, PARP and LC3-Ⅱ expressions were obviously higher(P<0.05). However, the apoptotic rates and p21, cycling D1, PARP and LC3-Ⅱ expressions of MDA-MB-231-shPRMT5 cells treated by 4nM and 8nM docetaxel were obviously lower(P<0.05). Conclusion: The overexpression of PRMT5 could increase the sensitivity of MDA-MB-231 cell to Docetaxel. PRMT5 might be the key point to predict the sensitivity of docetaxel treatment and the target of regulation of docetaxel drug resistance. |
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