Department of Gastroenterology, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Department of Encephalopathy, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, China.
Biomed Pharmacother. 2016 Aug;82:319-26. doi: 10.1016/j.biopha.2016.05.015. Epub 2016 May 24.
Melanoma is the most serious type of skin cancer because it is highly frequency of drug resistance and can spread earlier and more quickly than other skin cancers. The objective of this research was to investigate the anticancer effects of cryptotanshinone on human melanoma cells in vitro, and explored its mechanisms of action. Our results have shown that cryptotanshinone could inhibit cell proliferation in human melanoma cell lines A2058, A375, and A875 in a dose- and time-dependent manner. In addition, flow cytometry assay showed that cryptotanshinone inhibited the proliferation of human melanoma cell line A375 by blocking cell cycle progression in G2/M phase and inducing apoptosis in a concentration-dependent manner. Moreover, western blot analysis indicated that the occurrence of its apoptosis was associated with upregulation of cleaved caspases-3 and pro-apoptotic protein Bax while downregulation of anti-apoptotic protein Bcl-2. Meanwhile, cryptotanshinone could decrease the levels of reactive oxygen species (ROS). Furthermore, cryptotanshinone also blocked A375 cell migration and invasion in vitro which was associated with the downregulation with MMP-9. Taken together, these results suggested that cryptotanshinone might be a potential drug in human melanoma treatment by inhibiting proliferation, inducing apoptosis via ROS-mitochondrial apoptotic pathway and blocking cell migration and invasion.
黑色素瘤是最严重的皮肤癌类型,因为它具有很高的耐药频率,并且比其他皮肤癌更早、更快地扩散。本研究旨在探讨隐丹参酮在体外对人黑色素瘤细胞的抗癌作用,并探讨其作用机制。我们的研究结果表明,隐丹参酮能够以剂量和时间依赖的方式抑制人黑色素瘤细胞系 A2058、A375 和 A875 的细胞增殖。此外,流式细胞术检测结果表明,隐丹参酮通过阻滞细胞周期于 G2/M 期并呈浓度依赖性诱导细胞凋亡,从而抑制人黑色素瘤细胞系 A375 的增殖。此外,Western blot 分析表明,其凋亡的发生与 cleaved caspases-3 和促凋亡蛋白 Bax 的上调以及抗凋亡蛋白 Bcl-2 的下调有关。同时,隐丹参酮还可以降低活性氧物种 (ROS) 的水平。此外,隐丹参酮还可以通过下调 MMP-9 来抑制 A375 细胞的迁移和侵袭。综上所述,这些结果表明,隐丹参酮可能通过抑制增殖、通过 ROS-线粒体凋亡途径诱导凋亡以及阻断细胞迁移和侵袭,成为治疗人类黑色素瘤的一种潜在药物。