α-常春藤皂苷调控SREBP1/FASN通路抑制非小细胞肺癌的恶性表型
α-Hederin Regulates SREBP1/FASN Pathway and Inhibits Malignant Phenotype of Non-small Cell Lung Cancer
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摘要:目的 探讨α-常春藤皂苷对非小细胞肺癌细胞增殖和侵袭的调控作用及其相关分子机制。方法 采用梯度浓度α-常春藤皂苷分别处理A549和HCC-1833细胞24和48 h后, CCK8法检测细胞活力值(OD450nm)并计算半数抑制浓度(IC50)。根据IC50值将A549细胞和HCC-1833细胞分为空白对照组和α-常春藤皂苷组。EdU试剂盒检测细胞增殖, 流式细胞术检测细胞周期和细胞凋亡率, Transwell检测细胞迁移率, 划痕实验检测细胞侵袭率, Western blot检测SREBP1和FASN蛋白表达水平, 油红O染色检测细胞脂质积累。结果 肺癌细胞的存活率随α-常春藤皂苷的浓度升高显著降低, 48 h对应的A549细胞和HCC-1833细胞的IC50分别为15 μg/ml和25 μg/ml。与对照组相比, α-常春藤皂苷处理后, 细胞的增殖、迁移被显著抑制, 细胞阻滞于G1/S期, 细胞凋亡率增加, SREBP1和FASN的蛋白表达和细胞脂质积累都显著降低。结论 α-常春藤皂苷可抑制NSCLC细胞增殖、迁移, 诱导细胞凋亡, 使细胞阻滞于G1/S期, 通过下调SREBP1和FASN的表达, 减少细胞脂质积累, 阻碍非小细胞肺癌恶性进程。Abstract:Objective To explore the regulative effect of α-Hederin on the proliferation and invasion of NSCLC and investigate its related molecular mechanism.Methods After A549 and HCC-1833 cells were treated with a concentration gradient of α-Hederin for 24 and 48 h, the OD450nm was detected by using CCK8 assays, and the IC50 was calculated.The A549 and HCC-1833 cells were divided into the blank control and α-Hederin groups in accordance with IC50 values.Cell proliferation was detected by EdU assays, and cell cycle transformation and cell apoptosis were detected by flow cytometry.Cell mobility was detected by using Transwell and scratch assays.SREBP1 and FASN protein expression levels were detected through Western blot analysis, and cell lipid accumulation was detected via oil red O staining.Results The survival rate of lung cancer cells decreased significantly with the increase of α-Hederin concentration, and the IC50 values of A549 and HCC-1833 cells at 48 h were 15 and 25 μg/ml, respectively.Compared with the blank control group, cells proliferation and migration were significantly inhibited, cells were blocked in the G1/S phase, the apoptosis rate increased, and the protein expression and lipid accumulation of SREBP1/FASN significantly reduced after α-Hederin treatment.Conclusion α-Hederin can inhibit the proliferation and migration, G1/S phase transition and induce the apoptosis of NSCLC cells and hinder the malignant progression of NSCLC by downregulating the expression of SREBP1 and FASN and reducing the accumulation of cell lipids.
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