姜黄素通过调节糖代谢重编程抑制三阴性乳腺癌细胞的恶性表型

Curcumin Inhibits Malignant Phenotype of Triple Negative Breast Cancer Cells by Regulating Glucose Metabolism Reprogramming

目的探讨姜黄素(curcumin)对三阴性乳腺癌(Triple Negative Breast Cancer,TNBC)细胞增殖、迁移和凋亡的影响,并从糖代谢重编程关键靶点的改变角度阐明其作用机制。方法采用细胞活性检测试剂盒(Cell Counting Kit 8,CCK-8法)和Transwell法检测姜黄素对TNBC细胞MDA-MB-231(MB-231)增殖、迁移和侵袭的影响。流式细胞术和Western blot(WB)检测姜黄素对MB-231细胞凋亡和细胞周期阻滞的影响。实时定量聚合酶链式反应(Real Time-Quantitative Polymerase Chain Reaction,RT-qPCR)和WB法检测姜黄素对糖代谢重编程关键靶点的调控影响。结果姜黄素剂量依赖性的抑制MB-231细胞的增殖和迁移,显著增加细胞凋亡,并导致S期阻滞,同时也下调了MB-231细胞中糖代谢重编程关键靶点mRNA表达。WB结果显示,姜黄素也下调了抗凋亡蛋白表达(Bcl-2)和糖代谢重编程关键蛋白的表达,增加了促凋亡相关蛋白(Cleaved-Caspase3、Bax)的表达。结论姜黄素能明显抑制MB-231细胞的增殖和迁移,并促进其凋亡,作用机制可能与下调Bcl-2/Bax蛋白的表达,诱导肿瘤细胞凋亡,下调乳腺癌有氧糖酵解,调节乳腺癌糖代谢重编程有关。

Objective To investigate the effects of curcumin on the proliferation,migration and apoptosis of triple negative breast cancer(TNBC)cells,and to elucidate its mechanism from the perspective of changes in key targets of glucose metabolism reprogramming.Methods Cell Counting Kit 8(CCK-8 method)and Transwell method were used to detect the effects of curcumin on the proliferation,migration,and invasion of TNBC cells MDA-MB-231(MB-231).Flow cytometry and Western blot(WB)were used to detect the effects of curcumin on apoptosis and cell cycle arrest in MB-231 cells.Real Time Quantitative Polymerase Chain Reaction(RT qPCR)and WB methods were used to detect the regulatory effects of curcumin on key targets of glucose metabolism reprogramming.Results The results showed that curcumin dose-dependently inhibited the proliferation and migration of MB-231 cells,significantly increased cell apoptosis,and led to S-phase arrest.At the same time,it also downregulated the mRNA expression of key targets for glucose metabolism reprogramming in MB-231 cells.The WB results showed that curcumin also downregulated the expression of anti apoptotic protein(Bcl-2)and key proteins for glucose metabolism reprogramming,and increased the expression of pro apoptotic related proteins(Cleared Caspase3,Bax).Conclusion Curcumin can significantly inhibit the proliferation and migration of MB-231 cells,and promote their apoptosis.The mechanism may be related to down-regulation of Bcl-2/Bax protein expression,induction of tumor cell apoptosis,down-regulation of aerobic glycolysis in breast cancer,and regulation of glycometabolism reprogramming in breast cancer.