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

被引:7
|
作者
Ozman, Zeynep [1 ]
Guney Eskiler, Gamze [2 ]
Sekeroglu, Mehmet R. [3 ]
机构
[1] Bezmialem Vakif Univ, Fac Med, Dept Med Biochem, Istanbul, Turkey
[2] Sakarya Univ, Fac Med, Dept Med Biol, TR-54290 Sakarya, Turkey
[3] Sakarya Univ, Fac Med, Dept Med Biochem, Sakarya, Turkey
关键词
abemaciclib; apoptosis; atypical cell death; CDK4; 6; inhibitors; triple-negative breast cancer; CDK4/6; INHIBITION; DEATH;
D O I
10.1002/jbt.22858
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:11
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