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单羧酸转运蛋白1增强乳腺癌细胞对3-溴丙酮酸的敏感性

李其响 张配 刘芳 王先知 李璐 王仲崑 蒋琛琛 郑海伦 刘浩

南方医科大学学报2017,Vol.37Issue(5):588-593,6.
南方医科大学学报2017,Vol.37Issue(5):588-593,6.DOI:10.3969/j.issn.1673-4254.2017.05.04

单羧酸转运蛋白1增强乳腺癌细胞对3-溴丙酮酸的敏感性

Monocarboxylate transporter 1 enhances the sensitivity of breast cancer cells to 3-bromopvruvate in vitro

李其响 1张配 1刘芳 1王先知 1李璐 1王仲崑 1蒋琛琛 1郑海伦 2刘浩1

作者信息

  • 1. 蚌埠医学院药学院,安徽蚌埠233030
  • 2. 蚌埠医学院第一附属医院消化科,安徽蚌埠233030
  • 折叠

摘要

Abstract

Objective To investigate the role of monocarboxylate transporter 1 (MCT1) in enhancing the sensitivity of breast cancer cells to 3-bromopyruvate (3-BrPA).Methods The inhibitory effect of 3-BrPA on the proliferation of breast cancer cells was assessed with MTT assay,and brominated propidium bromide single staining flow cytometry was used for detecting the cell apoptosis.An ELISA kit was used to detect the intracellular levels of hexokinase II,lactate dehydrogenase,lactate,and adenosine triphosphate,and Western blotting was performed to detect the expression of MCT1.MDA-MB-231 cells were transiently transfected with MCT1 cDNA for over-expressing MCT1,and the effect of 3-BrPA on the cell proliferation and adenosine triphosphate level was deteced.Results 3-BrPA did not produce significant effects on the proliferation and apoptosis of MDA-MB-231 cells,and the cells treated with 200 μmol/L 3-BrPA for 24 h showed an inhibition rate and an apoptosis rate of only 8.72% and 7.8%,respectively.The same treatment,however,produced an inhibition rate and an apoptosis rate of 84.6% and 82.3% in MCF-7 cells,respectively.In MDA-MB-231 cells with MCT1 overexpression,200 μmol/L 3-BrPA resulted in an inhibition rate of 72.44%,significantly higher than that in the control cells (P<0.05);treatment of the cells with 25,50,100,and 200 μmol/L 3-BrPA for 6 h resulted in intracellular adenosine triphosphate levels of 96.98%,88.44%,43.3% and 27.56% relative to the control level respectively.Conclusion MCT1 can enhance the sensitivity of breast cancer cells to 3-BrPA possibly by transporting 3-BrPA into cells to inhibit cell glycolysis.

关键词

乳腺癌/3-溴丙酮酸/单羧酸转运蛋白1/糖酵解/瓦博格效应

Key words

breast cancer/3-BrPA/monocarboxylate transporter 1/glycolysis/Warburg effect

引用本文复制引用

李其响,张配,刘芳,王先知,李璐,王仲崑,蒋琛琛,郑海伦,刘浩..单羧酸转运蛋白1增强乳腺癌细胞对3-溴丙酮酸的敏感性[J].南方医科大学学报,2017,37(5):588-593,6.

基金项目

国家自然科学基金(81372899,81603155) (81372899,81603155)

安徽省教育厅重大项目(KJ2016SD39) (KJ2016SD39)

安徽省国际合作交流项目(1503062024) (1503062024)

安徽省高校省级自然科学研究项目(KJ2015A177) (KJ2015A177)

蚌埠医学院研究生科研创新计划项目(Byycxz1621)Supported by National Natural Science Fundation of China (81372899,81603155). (Byycxz1621)

南方医科大学学报

OA北大核心CSCDCSTPCDMEDLINE

1673-4254

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