1,6二磷酸果糖增强蛋白酶体抑制剂对人乳腺癌细胞MCF-7的抑瘤效应

Combination of Fructose-1,6-Diphosphate and Proteasome Inhibitor Enhances Inhibition of Cell Proliferation in Human MCF-7 Breast Cancer Cells

目的探讨抑制蛋白酶体活性是否可以诱导人乳腺癌细胞MCF-7的自我吞噬,1,6二磷酸果糖对自我吞噬的影响及自我吞噬对细胞增殖的作用。方法采用MTT法检测细胞增殖,蛋白质印迹检测自我吞噬相关蛋白LC3的表达。结果蛋白酶体抑制剂硼替佐米以剂量依赖方式抑制MCF-7细胞的增殖并诱导细胞的自我吞噬,但是,当1,6二磷酸果糖与硼替佐米联合应用后,可逆转硼替佐米诱导的自我吞噬并增强硼替佐米对MCF-7细胞的增殖抑制。结论蛋白酶体活性的抑制可诱导人乳腺癌细胞MCF-7的自我吞噬代偿性激活,1,6二磷酸果糖可抑制激活的自我吞噬,其与硼替佐米的联合应用可增强其抑瘤效应。

Objective To investigate whether inhibition proteasome can induce autophagy,effects of fructose-1,6-diphosphate（FDP） on autophagy and effects of autophagy on the fate of human breast cancer MCF-7 cells.Methods Cell viability was measured by MTT assay.Apoptosis was detected by flow cytometry.The expression of autophagy related proteins was determined by Western blot.Results MCF-7 cells proliferation was inhibited by proteasome inhibitor Bortezomib in a dose dependent manner and autophagy was activated in the same manner.However,when MCF-7 cells were co-treated with Bortezomib and FDP,it could lead the most significant inhibition of cell proliferation.Moreover,FDP blocked the increase of LC3-II protein expression induced by Bortezomib.Conclusion The inhibition of proteasome can induce autophagy in human breast cancer MCF-7 cells and FDP could inhibit autophagy induced by proteasome inhibitor.Combination of FDP and Bortezomib increases cell death.