Department of Dermatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China.
Hunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, 410008, Hunan, China.
Naunyn Schmiedebergs Arch Pharmacol. 2021 Apr;394(4):797-807. doi: 10.1007/s00210-020-01981-4. Epub 2020 Oct 3.
Resveratrol (RES) as a natural phytoalexin has anti-tumor effects on various cancers through its pro-apoptotic activities. Our aim was to determine that RES induces apoptosis in melanoma cells by regulating miR-492 resulting in decreased CD147 expression. We treated A375 and SK-MEL-28 melanoma cells via RES at different concentrations and time-points. The results have shown that the inhibition rate of A375 and SK-MEL-28 was significantly increased after RES treatment. Subsequently, we investigated cell apoptosis by flow cytometry, as well as detected apoptotic-associated proteins including PARP, Caspase-3, Bcl-2, and Bax by western blotting. Meanwhile, the expression of miR-492 and CD147 was analyzed. We found that RES remarkably induces apoptosis in melanoma cells, along with an upregulation of miR-492 and the inhibition of CD147 expression. Furthermore, the detection of luciferase reporter activity confirmed that miR-492 could target CD147 mRNA, and transfected with mimic miR-492 in cells reduced CD147 expression. We also performed the rescued experiment by using a miR-492 inhibitor in melanoma cells. The results showed that the ability of induced apoptosis by RES in melanoma cells was to be attenuated via inhibiting miR-492 expression resulting in CD147 augment. Finally, we determined that the effect of RES-induced apoptosis in melanoma cells is associated with, at least in part, its ability to regulate the miR-492/CD147 pathway.
白藜芦醇（RES）作为一种天然植物抗毒素，通过其促凋亡活性对各种癌症具有抗肿瘤作用。我们的目的是确定 RES 通过调节 miR-492 降低 CD147 表达从而诱导黑色素瘤细胞凋亡。我们用不同浓度和时间点的 RES 处理 A375 和 SK-MEL-28 黑色素瘤细胞。结果表明，RES 处理后 A375 和 SK-MEL-28 的抑制率显著增加。随后，我们通过流式细胞术研究细胞凋亡，并通过 Western blot 检测凋亡相关蛋白包括 PARP、Caspase-3、Bcl-2 和 Bax。同时，分析了 miR-492 和 CD147 的表达。我们发现 RES 可显著诱导黑色素瘤细胞凋亡，同时上调 miR-492 并抑制 CD147 表达。此外，通过荧光素酶报告基因活性检测证实 miR-492 可以靶向 CD147 mRNA，转染细胞中的 mimic miR-492 可降低 CD147 表达。我们还在黑色素瘤细胞中进行了 miR-492 抑制剂的挽救实验。结果表明，通过抑制 miR-492 表达导致 CD147 增加，从而减弱 RES 诱导黑色素瘤细胞凋亡的能力。最后，我们确定 RES 诱导黑色素瘤细胞凋亡的作用至少部分与其调节 miR-492/CD147 通路的能力有关。
