Investigation of simvastatin-induced apoptosis and cell cycle arrest in cancer stem cells of MCF-7
Investigation of simvastatin-induced apoptosis and cell cycle arrest in cancer stem cells of MCF-7
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DOI：
10.4103/0973-1482.146127
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发表时间：
2016-04-01
影响因子：
1.3
通讯作者：
Ostad, Seyed Nasser
中科院分区：
文献类型：
--
作者：
Afzali, Monireh;Vatankhah, Melody;Ostad, Seyed Nasser
背景：最近的研究表明他汀类药物的使用与降低癌症风险之间存在关联。此外，癌症干细胞（CSC）在肿瘤发生、进展和迁移中的重要性已在多种实体瘤中得到牢固确立。因此，有效靶向乳腺 CSC 有可能显着改善癌症治疗结果。目的：本研究旨在调查辛伐他汀对乳腺 CSC 的抗癌作用。设置和设计：在本研究中，从亲代细胞中分离出 MCF-7 CSC，并评估和比较辛伐他汀在两种细胞中的细胞毒性作用。对象和方法：通过流式细胞仪技术进行干细胞分离，评估辛伐他汀对干细胞活力、凋亡和细胞周期的影响，并与亲代细胞进行比较。使用的统计分析：使用单向方差分析（one.way ANOVA）分析结果，然后进行 Tukey.Kramer 后检验。 P<0.05被认为是显着的。结果：基于结果，辛伐他汀对CSC和亲代MCF-7细胞均显示出剂量依赖性细胞毒作用，而与亲代细胞相比，CSC中的凋亡诱导和非凋亡性程序性死亡的消除增加。此外，辛伐他汀显示 MCF-7 CSC 中 DNA 合成减少并诱导细胞周期停滞在 G1 期。结论：这一发现表明辛伐他汀对 MCF-7 CSC 具有特异性凋亡作用，可能为未来的体内和体外他汀类药物试验提供支持理由。
Context: Recent studies have shown the association between statins use and cancer risk reduction. Furthermore the importance of cancer stem cells (CSCs) in tumor initiation, progression and migration has been firmly established in a variety of solid tumors. Hence, the effective targeting of breast CSCs has a potential to improve cancer treatment outcome significantly. Aims: This study has been designed to investigation the anticancer effects of simvastatin on breast CSCs. Settings and Design: In this study, MCF-7 CSCs were isolated from parent cells and cytotoxic effects of simvastatin were evaluated and compared in both cells. Subjects and Methods: Stem cell isolation was done by flow cytometry technique and the effects of simvastatin on the stem cell viability, apoptosis and cell cycle were evaluated and compared with parent cells. Statistical Analysis Used: The results were analyzed using one.way ANOVA, followed by Tukey.Kramer posttest. The P 0.05 was considered as significant. Results: Based on the result, simvastatin shows dose-dependent cytotoxic effects on both CSCs and parent MCF-7 cells, whereas the apoptosis induction and the elimination of nonapoptotic programmed death were increased in CSC compared with parent cells. In addition, simvastatin showed the reduction in DNA synthesis and induced cell cycle arrest in the G1 phase in MCF-7 CSCs. Conclusions: This finding indicates that simvastatin with specific apoptotic effect on MCF-7 CSC may provide supporting reasons for future in vivo and in vitro statin trials.