Király József, Szabó Erzsébet, Fodor Petra, Fejes Zsolt, Nagy Béla, Juhász Éva, Vass Anna, Choudhury Mahua, Kónya Gábor, Halmos Gábor, Szabó Zsuzsanna
Department of Biopharmacy, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary.
Department of Pharmacology, Faculty of Pharmacy, University of Debrecen, 4032 Debrecen, Hungary.
Molecules. 2023 Sep 20;28(18):6725. doi: 10.3390/molecules28186725.
(1) Background: Shikonin, the main ingredient in Chinese herbal medicine, is described as a novel angiogenesis inhibitor, and its anticancer effects have already been studied. Shikonin and its derivatives induce apoptosis and suppress metastasis, which further enhance the effectiveness of chemotherapy. However, their mechanism of function has not been completely elucidated on human renal cancer cells. (2) Methods: In our study, CAKI-2 and A-498 cells were treated with increasing concentrations (2.5-40 µM) of shikonin, when colony formation ability and cytotoxic activity were tested. The changes in the expression of the main targets of apoptotic pathways were measured by RT-qPCR and Western blot. The intracellular levels of miR-21 and miR-155 were quantified by RT-qPCR. (3) Results: Shikonin exerted a dose-dependent effect on the proliferation of the cell lines examined. In 5 µM concentration of shikonin in vitro elevated caspase-3 and -7 levels, the proteins of the Ras/MAPK and PI3K/AKT pathways were activated. However, no significant changes were detected in the miR-21 and miR-155 expressions. (4) Conclusions: Our findings indicated that shikonin causes apoptosis of renal cancer cells by activating the Ras/MAPK and PI3K/AKT pathways. These effects of shikonin on renal cancer cells may bear important potential therapeutic implications for the treatment of renal cancer.
（1）背景：紫草素是中药的主要成分，被描述为一种新型血管生成抑制剂，其抗癌作用已得到研究。紫草素及其衍生物可诱导细胞凋亡并抑制转移，从而进一步增强化疗效果。然而，它们在人肾癌细胞上的作用机制尚未完全阐明。（2）方法：在我们的研究中，用浓度递增（2.5 - 40 μM）的紫草素处理CAKI - 2和A - 498细胞，同时检测集落形成能力和细胞毒性活性。通过RT - qPCR和蛋白质免疫印迹法检测凋亡途径主要靶点表达的变化。通过RT - qPCR定量miR - 21和miR - 155的细胞内水平。（3）结果：紫草素对所检测的细胞系增殖具有剂量依赖性作用。在体外5 μM浓度的紫草素作用下，半胱天冬酶 - 3和 - 7水平升高，Ras/MAPK和PI3K/AKT途径的蛋白质被激活。然而，miR - 21和miR - 155的表达未检测到显著变化。（4）结论：我们的研究结果表明，紫草素通过激活Ras/MAPK和PI3K/AKT途径导致肾癌细胞凋亡。紫草素对肾癌细胞的这些作用可能对肾癌治疗具有重要的潜在治疗意义。
