icariin和curcumol在前列腺癌miR-7/m-TOR/SREBP1途径上的自噬、铁死亡和脂质代谢影响
Effects of icariin and curcumol on autophagy, ferroptosis, and lipid metabolism based on miR-7/m-TOR/SREBP1 pathway on prostate cancer.
发表日期:2022 Dec 30
作者:
Wenjing Xu, Jin Ding, Bonan Li, Tiansong Sun, Xujun You, Qinghu He, Wen Sheng
来源:
BIOFACTORS
摘要:
本研究旨在探究淫羊藿苷(ICA)和青蒿醇对前列腺癌(PCa)细胞内和体外自噬、铁死亡和脂质代谢的影响和分子机制。我们分别给正常的前列腺上皮细胞RWPE-1和PCa细胞系DU145和PC-3进行了ICA和青蒿醇处理,在DU145和PC-3细胞中添加亚铁血红蛋白-1(Fer-1)或3-MA进行处理。另外,我们通过静默miR-7来证实ICA和青蒿醇对PCa细胞的机制。ICA和青蒿醇对RWPE-1细胞的存活率无明显影响,但对DU145和PC-3细胞有显著差异。ICA和青蒿醇处理后,PCa细胞的增殖被抑制,细胞凋亡、活性氧(ROS)水平和miR-7表达增加,ICA和青蒿醇联合处理具有更显著的效果。ICA和青蒿醇处理诱导PCa细胞的自噬和铁死亡,而si-miR-7逆转了ICA和青蒿醇对自噬和铁死亡的影响。miR-7靶向mTOR并调节PCa细胞中mTOR / SREBP1 通路的表达。ICA和青蒿醇可能通过影响SREBP1影响PCa细胞的脂质代谢。此外,ICA和青蒿醇在PCa细胞中自噬、铁死亡和脂质代谢方面的影响和机制在体内得到验证。ICA和青蒿醇通过协同调节miR-7 / mTOR / SREBP1通路诱导PCa细胞的自噬和铁死亡,影响脂质代谢。© 2022国际生物化学与分子生物学联合会。
This study aimed to investigate the effects and underlying molecular mechanisms of icariin (ICA) and curcumol on autophagy, ferroptosis, and lipid metabolism in prostate cancer (PCa), in vitro and in vivo. Normal prostate epithelial cells RWPE-1 and PCa cell lines DU145 and PC-3 were treated with ICA and curcumol. Ferrostatin-1 (Fer-1) or 3-MA was added to treat DU145 and PC-3 cells. In addition, we knocked down miR-7. The mechanism of ICA and curcumol in PCa cells after the knockdown of miR-7 was verified by in vitro nude mice tumorigenesis experiments. ICA and curcumol had no significant effect on the viability of RWPE-1 cells, but there was a significant difference between DU145 and PC-3 cells. After treatment with ICA and curcumol, the proliferation of PCa cells was inhibited, apoptosis, reactive oxygen species (ROS) levels, and miR-7 expression were increased. The combined treatment of ICA and curcumol had a more significant effect. ICA and curcumol treatment induced autophagy and ferroptosis in PCa cells, and si-miR-7 reversed the effects of ICA and curcumol on autophagy and ferroptosis. MiR-7 targeted mTOR and regulated the expression of the mTOR/SREBP1 pathway in PCa cells. ICA and curcumol may affect the lipid metabolism of PCa cells by affecting SREBP1. In addition, the effects and mechanisms of ICA and curcumol on autophagy, ferroptosis, and lipid metabolism in PCa cells were verified in vivo. ICA and curcumol synergistically regulated the miR-7/mTOR/SREBP1 pathway to induce autophagy and ferroptosis in PCa cells and affected lipid metabolism.© 2022 International Union of Biochemistry and Molecular Biology.