硼替佐米单药或联合氨氯地平诱导人乳腺癌细胞焦亡  

Bortezomib alone or in combination with amlodipine induces pyroptosis in human breast cancer cells

作　　者：赵小霞 兰凯 ZHAO Xiao-xia;LAN Kai(Tianjin Huanhu Hospital,Tianjin 300350,China)

机构地区：[1]天津市环湖医院药剂科,天津300350

出　　处：《中国处方药》2024年第3期34-38,共5页Journal of China Prescription Drug

摘　　要：目的研究硼替佐米(Bor)单药或联合氨氯地平(Ad)对人乳腺癌细胞焦亡的作用。方法用不同浓度Bor处理MCF-7细胞,采用MTT实验检测细胞活力,倒置显微镜相差观察细胞焦亡形态变化,检测LDH释放量,流式细胞术检测焦亡细胞,Western blot实验检测焦孔素(GSDM)E蛋白。此外,Bor联合Ad共同处理MCF-7细胞,采用Chou-Talalay分析联合用药,倒置显微镜观察细胞形态学变化,检测LDH释放量,流式细胞术检测焦亡细胞,Western blot实验检测GSDME蛋白、抗凋亡蛋白Bcl-2和PARP蛋白表达。结果与对照组细胞相比,Bor浓度依赖性地抑制MCF-7细胞增殖,上调GSDME-N蛋白表达(P<0.001),诱导细胞焦亡;Bor联合Ad协同抑制MCF-7细胞增殖,降低Bcl-2蛋白(P<0.01),升高GSDME-N蛋白(P<0.001),同时升高Cleaved-PARP蛋白表达,协同诱导细胞焦亡和凋亡。结论Bor单药诱导乳腺癌细胞焦亡,抑制细胞增殖,具有很好的抗肿瘤作用。Bor联合Ad可能通过抑制Bcl-2蛋白表达诱导乳腺癌细胞焦亡和细胞凋亡,协同抑制细胞增殖,具有治疗乳腺癌的潜力。Objective To study the effect of bortezomib alone or in combination with amlodipine on pyroptosis of human breast cancer.Methods The human breast cancer line MCF-7 cells were treated with different concentrations of Bor.The cell proliferation was determined by MTT.The morphological change of cell pyroptosis was observed under inverted microscope,and LDH release is detected.The flow cytometry was used to detect pyroptosis cells,and Western blot was used to detect the protein expression of GSDME.In addition,Bor combined with Ad to treat MCF-7 cells,the combination index using Chou-Talalay analysis.The morphological change of cell pyroptosis was observed under inverted microscope,the pyroptosis cells were detected by flow cytometry,and the protein expression of GSDME and Bcl-2 were used to detect by Western blot.Results Compared with the control group,Bor concentration dependently inhibited the proliferation of MCF-7 cells,up-regulated the expression of GSDME-N protein(P<0.001)and induced the cell pyroptosis.Bor combined with Ad synergistically inhibited the proliferation of MCF-7 cells,down-regulated the expression of Bcl-2 protein(P<0.01),up-regulated the expression of GSDME-N protein(P<0.001)and Cleaved-PARP protein,and synergistically induced the cell pyroptosis.Conclusion Bor can induce pyroptosis of breast cancer cells,inhibit cell proliferation,and has a good anti-tumor effect.Bor combined with Ad may induce pyroptosis and apoptosis of breast cancer cells by inhibiting the expression of Bcl-2 protein,and synergistically inhibit cell proliferation,which has the potential of combined treatment of breast cancer.

关 键 词：人乳腺癌 硼替佐米 氨氯地平 细胞焦亡 

分 类 号：R96[医药卫生—药理学]