Wang Peng, Wang Chun, Liu Chunying
College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning 110847, P.R. China.
Oncol Lett. 2021 Jan;21(1):59. doi: 10.3892/ol.2020.12321. Epub 2020 Nov 19.
Skin cancer is the deadliest type of malignant disease and causes primary mortality worldwide. Dioscin, which exists in medicinal plants, has potent anticancer effects. However, its effects on skin cancer remain unknown. In the present study, the activity and mechanism of dioscin on the human skin cancer A431 cell line were investigated, MTT, colony formation, Transwell, wound-healing, TUNEL, Comet, immunofluorescence and western blot assays were used to assess the effects of dioscin on A431 cells. The results of MTT, colony formation, Transwell and wound-healing assays revealed that dioscin suppressed proliferation, colony formation and invasion of the cancer cells. TUNEL and comet assays demonstrated that dioscin exhibited significant effects on cell apoptosis and DNA damage. Investigations into the mechanism revealed that the expression levels of phosphorylated Ataxia telangiectasia-mutated (ATM) were considerably activated by dioscin, which significantly upregulated the expression levels of p53 to activate mitochondrial apoptosis signaling. Furthermore, the expression levels of BAX, cleaved caspase-3/9 and cleaved poly (ADP-ribose) polymerase were upregulated, and the expression levels of BCL-2 were downregulated by dioscin. Additionally, dioscin markedly downregulated the expression levels of matrix metalloproteinase 2 (MMP2), MMP9, RHO and cdc42, which are all associated with tumor invasion. In addition, p53-small interfering RNA transfection experiments indicated that dioscin exhibited excellent activity against skin cancer by decreasing p53 expression. Overall, the present results suggested that dioscin inhibited skin cancer cell proliferation via adjusting ATM/p53-mediated cell apoptosis, migration and DNA damage, which should be considered as a potential option for future treatments of skin cancer.
皮肤癌是最致命的恶性疾病类型，在全球范围内导致原发性死亡。存在于药用植物中的薯蓣皂苷具有强大的抗癌作用。然而，其对皮肤癌的影响尚不清楚。在本研究中，研究了薯蓣皂苷对人皮肤癌A431细胞系的活性和作用机制，采用MTT、集落形成、Transwell、伤口愈合、TUNEL、彗星实验、免疫荧光和蛋白质印迹分析来评估薯蓣皂苷对A431细胞的影响。MTT、集落形成、Transwell和伤口愈合实验结果显示，薯蓣皂苷抑制癌细胞的增殖、集落形成和侵袭。TUNEL和彗星实验表明，薯蓣皂苷对细胞凋亡和DNA损伤有显著影响。对作用机制的研究表明，薯蓣皂苷可显著激活磷酸化共济失调毛细血管扩张突变蛋白（ATM）的表达水平，从而显著上调p53的表达水平以激活线粒体凋亡信号。此外，薯蓣皂苷上调BAX、裂解的半胱天冬酶-3/9和裂解的聚（ADP-核糖）聚合酶的表达水平，并下调BCL-2的表达水平。此外，薯蓣皂苷显著下调与肿瘤侵袭相关的基质金属蛋白酶2（MMP2）、MMP9、RHO和cdc42的表达水平。此外，p53小干扰RNA转染实验表明，薯蓣皂苷通过降低p53表达对皮肤癌表现出优异的活性。总体而言，目前的结果表明，薯蓣皂苷通过调节ATM/p53介导的细胞凋亡、迁移和DNA损伤来抑制皮肤癌细胞增殖，这应被视为未来皮肤癌治疗的潜在选择。
