毒胡萝卜素抑制卵巢癌细胞的增殖、迁移和侵袭并诱导细胞凋亡  

Thapsigargin inhibits proliferation,migration,and invasion of ovarian cancer cells and induces apoptosis

作　　者：沈帆 王丽丽[1] 赵杨[1] SHEN Fan;WANG Lili;ZHAO Yang(Department of Gynecology,The First Hospital,China Medical University,Shenyang 110001,China)

机构地区：[1]中国医科大学附属第一医院妇科,沈阳110001

出　　处：《中国医科大学学报》2020年第5期442-447,453,共7页Journal of China Medical University

摘　　要：目的探讨毒胡萝卜素对卵巢癌细胞增殖、迁移、侵袭及凋亡的影响及可能的作用机制。方法用不同浓度的毒胡萝卜素处理卵巢癌细胞系OVCAR3和A2780。采用噻唑蓝(MTT)法检测细胞活力,流式细胞术检测细胞凋亡及细胞内Ca^2+的变化,细胞划痕和侵袭实验检测细胞迁移及侵袭能力的变化。采用实时荧光定量PCR(qR T-PCR)技术和Western blotting检测相关基因蛋白的表达。结果不同浓度的毒胡萝卜素能够降低卵巢癌细胞系OVCAR3(0.03125~1.0μmol/L)和A2780(0.0625~2.0μmol/L)的细胞活力,且呈剂量依赖性。选取最适浓度进行相关实验,结果显示,毒胡萝卜素能够促进卵巢癌细胞凋亡,增加细胞质内Ca^2+的浓度,降低细胞的迁移及侵袭能力。此外,毒胡萝卜素处理后,肌浆/内质网Ca^2+-ATP酶2、血管内皮生长因子A、B细胞淋巴瘤2、SURVIVIN、B细胞淋巴瘤XL蛋白的表达水平降低,C/EBP同源蛋白表达水平升高。结论毒胡萝卜素可能通过增加细胞内Ca^2+的浓度诱导卵巢癌细胞凋亡,抑制卵巢癌细胞的增殖、迁移及侵袭。Objective To investigate the effect and possible mechanism of action of thapsigargin in ovarian epithelial cancer.Methods Ovarian cancer cell lines,OVCAR3 and A2780,were treated with different concentrations of thapsigargin.Cell viability was detected using the MTT assay.Apoptosis and changes in intracellular Ca^2+were detected by flow cytometry.Cell scratch and invasion tests were performed to detect changes in cell migration and invasion,respectively.Real-time quantitative PCR and Western blotting were used to detect the expression of related proteins.Results We found that different concentrations of thapsigargin reduced the viability of OVCAR3(0.03125 to 1.0μmol/L)and A2780(0.0625 to 2.0μmol/L)cells in a dose-dependent manner.We selected an optimal concentration of thapsigargin for all subsequent experiments.Thapsigargin promoted apoptosis,increased the concentration of cytoplasmic Ca^2+,and reduced the migration and invasion ability of ovarian cancer cells.In addition,thapsigargin treatment reduced the expression of SERCA2,vascular endothelial growth factor A,B-cell lymphoma-2,SURVIVIN,and B-cell lymphoma-XL,and increased the expression of C/EBPhomologous protein.Conclusion Thapsigargin may inhibit proliferation,migration,and invasion and induce apoptosis in ovarian cancer cells by increasing the concentration of intracellular Ca^2+.

关 键 词：毒胡萝卜素 卵巢上皮癌 肌浆/内质网Ca^2+-ATP酶2 

分 类 号：R737.31[医药卫生—肿瘤]