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[摘要]
[摘 要] 目的:探讨吉马酮(GM)调控环鸟苷酸-腺苷酸合成酶(cGAS)-干扰素基因刺激因子(STING)信号通路对前列腺癌 (PCa)细胞增殖、迁移、侵袭及凋亡的影响。方法:将PCa细胞PC3随机分为对照(正常培养)组,L-GM组、M-GM组、H-GM组 (分别经120、240、480 μmol/L GM处理)和GM + RU.521组(经480 μmol/L GM + 1 μmol/L cGAS抑制剂RU.521处理)。EdU染色 和CCK-8法、划痕实验、Transwell实验、流式细胞术分别检测GM对PC3细胞增殖、迁移、侵袭和凋亡的影响,WB法检测GM对 PC3细胞中cGAS和STING蛋白表达的影响。结果:与对照组比较,L-GM、M-GM、H-GM组EdU阳性细胞率、细胞增殖活力、划 痕愈合率、侵袭细胞数均显著降低(均P < 0.05),细胞凋亡率升高(P < 0.05),cGAS和STING蛋白表达显著上调,且均呈浓度依赖 性(均P < 0.05);与H-GM组比较,GM + RU.521组EdU阳性细胞率、细胞增殖活力、划痕愈合率和侵袭细胞数均显著升高(均 P < 0.05),细胞凋亡率降低(P < 0.05),cGAS和STING蛋白表达显著下调(均P < 0.05)。结论:GM通过激活cGAS-STING信号 通路抑制PCa细胞增殖、迁移、侵袭并促进凋亡。
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[Abstract]
[Abstract] Objective: To investigate the effects of germacrone (GM) regulation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway on the proliferation, migration, invasion and apoptosis of prostate cancer (PCa) cells. Methods: PCa PC3 cells were randomly separated into the control group (normal culture), the L-GM, the M-GM, the H-GM groups (each treated with 120, 240, 480 μmol/L GM respectively), and the GM + RU.521 group (treated with 480 μmol/L GM + 1 μmol/L cGAS inhibitor RU.521). EdU staining, CCK-8 assay, scratch assay, Transwell assay, and flow cytometry were applied to detect the effects of GM on the proliferation, migration, invasion, and apoptosis of PC3 cells, respectively. WB assay was used to detect the effects of GM on the expressions of cGAS and STING proteins in PC3 cells. Results: Compared with those in the control group, the rate of EdU-positive cells, cell proliferation activity, scratch healing rate, and the number of invasive cells in the L-GM, M-GM, and H-GM groups were significantly reduced (all P < 0.05); the apoptosis rate increased (P < 0.05); the expressions of cGAS and STING proteins were significantly upregulated, and were concentration-dependent (all P < 0.05). Compared with those in the H-GM group, the rate of EdU positive cells, cell proliferation activity, scratch healing rate and the number of invasive cells in the GM + RU.521 group were significantly elevated (all P < 0.05); the cell apoptosis rate decreased (P < 0.05); and the expressions of cGAS and STING proteins were significantly downregulated (all P < 0.05). Conclusion: GM inhibits the proliferation, migration, invasion and promotes the apoptosis of PCa cells by activating the cGAS-STING signaling pathway.
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