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体外阿贝西利对三阴性乳腺癌细胞的治疗作用。

In vitro therapeutic effects of abemaciclib on triple-negative breast cancer cells.

机构信息

Department of Medical Biochemistry, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.

Department of Medical Biology, Faculty of Medicine, Sakarya University, Sakarya, Turkey.

出版信息

J Biochem Mol Toxicol. 2021 Sep;35(9):e22858. doi: 10.1002/jbt.22858. Epub 2021 Jul 26.

Abstract

The cyclin-dependent kinases 4 and 6 have led to a significant improvement in the treatment of hormone-receptor-positive breast cancer. However, the therapeutic potential of abemaciclib in triple-negative breast cancer (TNBC) has not been definitively elucidated. Therefore, the objective of this study was to investigate abemaciclib mediated antiproliferative effects on MDA-MB-231 and MDA-MB-468 TNBC and MCF-10A cell line through annexin V, cell cycle, caspase-3, reverse transcription-polymerase chain reaction analysis, acridine orange, and DAPI staining, for the first time. In addition, the autophagy-related cell death was assessed by autophagy-LC3 assay and acidic vesicular organelles staining. Our findings demonstrated that abemaciclib treatment resulted in significant apoptotic cell death in TNBC cells via G0/G1 arrest, chromatin condensation, the upregulation of caspase-3 and Bax levels, and the downregulation of Bcl-2. However, the formation of a large number of cytoplasmic vacuoles was not associated with autophagy. Therefore, abemaciclib treatment could be an effective treatment for TNBC. However, further studies are needed to elucidate the molecular mechanism of abemaciclib-induced apoptotic as well as atypical cell death derived from lysosomes in TNBC.

摘要

细胞周期蛋白依赖性激酶 4 和 6 显著改善了激素受体阳性乳腺癌的治疗效果。然而,阿贝西利在三阴性乳腺癌(TNBC)中的治疗潜力尚未得到明确阐明。因此,本研究的目的是首次通过 Annexin V、细胞周期、Caspase-3、逆转录-聚合酶链反应分析、吖啶橙和 DAPI 染色,研究阿贝西利对 MDA-MB-231 和 MDA-MB-468 TNBC 和 MCF-10A 细胞系的增殖抑制作用。此外,通过自噬 LC3 测定法和酸性囊泡细胞器染色评估自噬相关的细胞死亡。我们的研究结果表明,阿贝西利治疗通过 G0/G1 期阻滞、染色质浓缩、Caspase-3 和 Bax 水平上调以及 Bcl-2 水平下调,导致 TNBC 细胞发生显著的凋亡性细胞死亡。然而,大量细胞质空泡的形成与自噬无关。因此,阿贝西利治疗可能是 TNBC 的一种有效治疗方法。然而,需要进一步的研究来阐明阿贝西利诱导的 TNBC 细胞凋亡和溶酶体来源的非典型细胞死亡的分子机制。

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