3-溴丙酮酸联合阿霉素对乳腺癌细胞增殖及凋亡的影响
Effect of 3-bromopyruvate combined with adriamycin on proliferation and apoptosis of human breast carcinoma cells in vitro
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摘要: 目的:研究3-溴丙酮酸(3-BRPA)联合阿霉素(ADM)对乳腺癌细胞MDA-MB-231增殖及凋亡的影响。方法:采用3-BRPA 80、160、320mol/L作用于MDA-MB-231乳腺癌细胞18 h后,测定其对细胞内ATP的影响;分别用3-BRPA 10、20、40、80、160mol/L和ADM 0.75、1.5、3、6、12mol/L,以及3-BRPA 80mol/L与ADM 0.75、1.5、3、6、12mol/L合用作用于MDA-MB-231乳腺癌细胞24、48和72 h后,MTT法检测乳腺癌细胞MDA-MB-231增殖情况;3-BRPA 80mol/L组、ADM0.75mol/L组以及3-BRPA 80mol/L与ADM 0.75mol/L合用组作用于乳腺癌细胞MDA-Mb-231 24 h后,利用碘化丙啶染色,流式细胞仪检测其诱导乳腺癌细胞凋亡的影响;采用3-BRPA 16mol/L、ADM 0.2mol/L以及3-BRPA 16mol/L与ADM0.2mol/L合用作用于乳腺癌细胞MDA-MB-231,5 d后观察对集落克隆形成的影响。结果:3-BRPA对乳腺癌细胞MDA-MB-231 ATP的生成有抑制作用;3-BRPA联合ADM后可明显增强ADM的细胞毒性作用;3-BRPA 80mol/L与ADM 0.75mol/L合用组诱导乳腺癌细胞MDA-MB-231 24 h凋亡率为39.6%,均显著高于对照组、3-BRPA单用组和ADM单用组(P0.01);3-BRPA增强ADM对乳腺癌细胞MDA-MB-231集落克隆形成的抑制作用。结论:3-BRPA可以增强ADM对乳腺癌细胞MDAMB-231增殖的抑制作用以及增强ADM诱导乳腺癌细胞凋亡的作用。Abstract: Objective:To investigate the effect of 3-Bromopyruvate(3-BrPA) combined with adriamycin(ADM) on proliferation and apoptosis of human breast carcinoma cells in vitro.Methods:The effects of 3-BrPA at 80,160 and 320 mol/L on ATP production of MDA-MB-231 breast cancer cells were detected.The growth inhibition effect was detected by MTT assay which induced by 3-BrPA(10,20,40,80,160 mol/L),adriamycin(0.75,1.5,3,6,12 mol/L) and 3-BrPA at 80 mol/L combined with adriamycin(0.75,1.5,3,6,12 mol/L) for 24 h,48 h and 72 h in MDA-MB-231 breast cancer cells.Cells were treated with 3-BrPA (80 mol/L),adriamycin(0.75 mol/L) and 3-BrPA(80 mol/L) combined with adriamycin(0.75 mol/L) for 24 hours,the apoptotic cells were detected using propidium iodide staining by flow cytometry.Cells were treated with 3-BrPA(16 mol/L),adriamycin(0.2 mol/L) and 3-BrPA(16 mol/L) combined with adriamycin(0.5 mol/L) for 5 days,the colony formation was detected by crystal violet staining method.Results:3-BrPA inhibited the formation of ATP in MDA-MB-231 breast cancer cells; 3-BrPA combined with ADM significantly enhanced the cytotoxicity of ADM.When MDA-MB-231 breast cancer cells were treated with 3-BrPA at 80 mol/L combined with ADM at 0.75 mol/L,the apoptosis rate was 39.6%,which was significantly higher than that in control group,3-BrPA group and ADM group(P0.01).3-BrPA enhanced the inhibitory effect of ADM on colony formation of MDA-MB-231 breast cancer cells.Conclusions:3-BrPA can enhance the inhibitory effect of adriamycin on proliferation and apoptosis of MDA-MB-231 breast cancer cells.
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Key words:
- breast neoplasm /
- 3-brominepyruvate /
- adriamycin /
- hexokinase inhibitor /
- glycolysis
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