背景:本研究调查了丹酚酸的影响,来源于丹参,黑色素瘤细胞生长。具体来说,我们评估了丹酚酸A(SalA)调节黑色素瘤细胞增殖的能力。
方法:我们使用人黑色素瘤A2058和A375细胞系,通过测量溴脱氧尿苷掺入和乳酸脱氢酶释放来研究SalA对细胞增殖和死亡的影响。我们使用水溶性四唑盐-1(WST-1)线粒体染色和碘化丙啶评估了细胞活力和周期进展。此外,我们使用磷酸激酶阵列来研究细胞内激酶磷酸化,通过蛋白质印迹分析特异性地测量SalA对检查点激酶-2(Chk-2)的影响。
结果:SalA剂量响应地抑制A2058和A375细胞的生长,并在G2/M期诱导细胞周期停滞。值得注意的是,SalA选择性诱导Chk-2磷酸化而不影响Chk-1,从而降解Chk-2调节的基因Cdc25A和Cdc2。然而,SalA不影响Chk1-Cdc25C通路。
结论:丹酚酸,尤其是萨尔A,通过诱导Chk-2磷酸化和破坏G2/M检查点调节来有效阻碍黑色素瘤细胞生长。
BACKGROUND: This study investigated the impact of salvianolic acids, derived from Danshen, on melanoma cell growth. Specifically, we assessed the ability of salvianolic acid A (Sal A) to modulate melanoma cell proliferation.
METHODS: We used human melanoma A2058 and A375 cell lines to investigate the effects of Sal A on cell proliferation and death by measuring bromodeoxyuridine incorporation and lactate dehydrogenase release. We assessed cell viability and cycle progression using water soluble tetrazolium salt-1 (WST-1) mitochondrial staining and propidium iodide. Additionally, we used a phospho-kinase array to investigate intracellular kinase phosphorylation, specifically measuring the influence of Sal A on checkpoint kinase-2 (Chk-2) via western blot analysis.
RESULTS: Sal A inhibited the growth of A2058 and A375 cells dose-responsively and induced cell cycle arrest at the G2/M phase. Notably, Sal A selectively induces Chk-2 phosphorylation without affecting Chk-1, thereby degrading Chk-2-regulated genes Cdc25A and Cdc2. However, Sal A does not affect the Chk1-Cdc25C pathway.
CONCLUSIONS: Salvianolic acids, especially Sal A, effectively hinder melanoma cell growth by inducing Chk-2 phosphorylation and disrupting G2/M checkpoint regulation.