Kaempferol suppresses proliferation and induces apoptosis and DNA damage in human gallbladder cancer cells through the CDK4/CDK6/cyclin D1 pathway.

IF 3.3 4区医学 Q1 Medicine

European review for medical and pharmacological sciences Pub Date : 2021-02-01 DOI:10.26355/eurrev_202102_24836

Z-Q Liu, G-L Yao, J-M Zhai, D-W Hu, Y-G Fan

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引用次数: 5

Abstract

Objective: Kaempferol has been reported to play an anti-tumor role in various human cancers, while its role in gallbladder cancer (GBC) is unclear.

Materials and methods: We found that kaempferol significantly inhibited the growth, invasion and migration, meanwhile induced apoptosis through cells arrested at G0/G1 phase of GBC cell lines, including GBC-SD and SGC996 cells in vitro.

Results: Kaempferol promoted the release of cytochrome C from the mitochondria to cytoplasm, the activation of c-caspase-3 and c-caspase-9 and increased the expression levels of pro-apoptotic factor Bax, meanwhile decreased the expression levels of anti-apoptotic factor Bcl-2. In addition, the expression levels of CDK4, CDK6 and cyclin D1, which are members of the CDK4/CDK6/cyclin D1 signaling pathway, were also decreased by kaempferol. Moreover, kaempferol could efficiently prevent tumor progression of GBC in the xenograft in vivo.

Conclusions: Our results demonstrated that kaempferol suppressed GBC progression through activation of the CDK4/CDK6/cyclin D1 signaling pathway, suggesting that it might be a potential anti-tumor agent for clinical treatment of GBC.

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山奈酚通过CDK4/CDK6/cyclin D1通路抑制人胆囊癌细胞增殖、诱导细胞凋亡和DNA损伤。

目的:山奈酚已被报道在多种人类癌症中具有抗肿瘤作用，但其在胆囊癌(GBC)中的作用尚不清楚。材料与方法:我们发现山奈酚能显著抑制GBC细胞系(包括GBC- sd和SGC996细胞)G0/G1期阻滞细胞的生长、侵袭和迁移，同时诱导细胞凋亡。结果:山奈酚可促进细胞色素C从线粒体向细胞质释放，激活C -caspase-3和C -caspase-9，提高促凋亡因子Bax的表达水平，降低抗凋亡因子Bcl-2的表达水平。此外，山奈酚也降低了CDK4/CDK6/cyclin D1信号通路成员CDK4、CDK6和cyclin D1的表达水平。山奈酚在体内可有效阻止异种移植物GBC的肿瘤进展。结论:我们的研究结果表明山奈酚通过激活CDK4/CDK6/cyclin D1信号通路抑制GBC的进展，提示它可能是一种潜在的抗肿瘤药物用于GBC的临床治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European review for medical and pharmacological sciences 医学-药学

CiteScore

5.30

自引率

6.10%

发文量

906

审稿时长

2-4 weeks

期刊介绍： European Review for Medical and Pharmacological Sciences, a fortnightly journal, acts as an information exchange tool on several aspects of medical and pharmacological sciences. It publishes reviews, original articles, and results from original research. The purposes of the Journal are to encourage interdisciplinary discussions and to contribute to the advancement of medicine. European Review for Medical and Pharmacological Sciences includes: -Editorials- Reviews- Original articles- Trials- Brief communications- Case reports (only if of particular interest and accompanied by a short review)