Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan Province, China.
Eur Rev Med Pharmacol Sci. 2021 Feb;25(3):1311-1321. doi: 10.26355/eurrev_202102_24836.
Kaempferol has been reported to play an anti-tumor role in various human cancers, while its role in gallbladder cancer (GBC) is unclear.
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.
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.
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.
山奈酚已被报道在多种人类癌症中发挥抗肿瘤作用，但其在胆囊癌（GBC）中的作用尚不清楚。
我们发现山奈酚可显著抑制 GBC 细胞系，包括 GBC-SD 和 SGC996 细胞的体外生长、侵袭和迁移，同时通过将细胞阻滞在 G0/G1 期诱导细胞凋亡。
山奈酚促进细胞色素 C 从线粒体释放到细胞质，激活 c-caspase-3 和 c-caspase-9，并增加促凋亡因子 Bax 的表达水平，同时降低抗凋亡因子 Bcl-2 的表达水平。此外，山奈酚还可降低 CDK4/CDK6/细胞周期蛋白 D1 信号通路成员 CDK4、CDK6 和细胞周期蛋白 D1 的表达水平。此外，山奈酚可有效防止体内异种移植 GBC 的肿瘤进展。
我们的研究结果表明，山奈酚通过激活 CDK4/CDK6/细胞周期蛋白 D1 信号通路抑制 GBC 进展，提示其可能成为治疗 GBC 的潜在抗肿瘤药物。
