维生素E琥珀酸酯诱导HER-2过表达乳腺癌细胞凋亡机制的研究

The apoptosis effect of vitamin E succinate on human HER-2 over-expression breast cancer cells

目的:探讨维生素E琥珀酸酯(vitamin E succinate,VES)对HER-2过表达乳腺癌细胞的生长抑制和诱导凋亡作用。方法:MTT法测定VES对乳腺癌MDA-MB-231和MDA-MB-453细胞增殖的抑制作用,应用Western blot法筛选HER-2过表达乳腺癌细胞系,同时检测VES处理后GSK-3、NF-κBp65、caspase 9蛋白在乳腺癌MDA-MB-231和MDA-MB-453细胞中的表达水平,划痕实验与侵袭实验观察VES对乳腺癌细胞体外迁移能力的影响,流式细胞术检测VES对乳腺癌细胞凋亡的作用。结果:VES处理后GSK-3、NF-κBp65、caspase 9蛋白在乳腺癌MDA-MB-453细胞中的表达明显高于在乳腺癌MDA-MB-231细胞中的表达,VES作用于HER-2低表达乳腺癌细胞使其迁移及侵袭能力明显增强,却能够抑制HER-2高表达乳腺癌细胞的迁移及侵袭。VES以直接杀伤方式作用MDA-MB-231细胞,而对MDA-MB-453则以诱导细胞凋亡方式杀伤,VES使HER-2高表达乳腺癌MDA-MB-453细胞发生G_1/G_0期阻滞。结论:VES促进乳腺癌细胞凋亡是通过影响多条信号传导途径完成的,VES作用于不同HER-2表达乳腺癌细胞其迁移及侵袭能力明显不同,其机制与细胞表面蛋白表达有关。

Objective: To observe the apoptosis effect of vitamin E succinate( VES) on the growth and proliferation of HER-2 over-expression breast cancer cells in vitro. Methods: MTT assay was used to detect the growth inhibition. Western blot was used to screening HER-2 over-expression of breast cancer cell lines and detect the expression satus of GSK-3,NF-κBp65 and caspase 9 in MDA-MB-231 and MDA-MB-453 cell. To observe the migration ability of VES by Transwell assay and Wound-healing for breast cancer cells in vitro,and flow cytometry to detect the effect of VES on apoptosis of breast cancer cells. Results: After treatment,The expression of GSK-3,NF-κBp65 and caspase 9 protein in the breast cancer MDA-MB-453 cells was significantly higher than that in the breast cancer MDA-MB-231 cells. The effect of VES on MDA-MB-231 breast cancer cells significantly enhanced its migration and invasion ability,while inhibited the migration and invasion of MDA-MB-453 cells. VES was used to kill MDA-MB-231 cells directly,and MDA-MB-453 to induce apoptosis. VES had a G1/G0 block in the high expression of breast cancer MDA-MB-453. Conclusion: VES to promote breast cancer cells apoptosis is completed by influencing the multiple signal transduction pathway. VES on different HER-2 over-expression breast cancer cell migration and invasion ability are obviously different,and its mechanism is related to the cell surface protein expression.