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

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、320μmol/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、160μmol/L和ADM 0.75、1.5、3、6、12μmol/L,以及3-BrPA 80μmol/L与ADM 0.75、1.5、3、6、12μmol/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 80μmol/L组、ADM0.75μmol/L组以及3-BrPA 80μmol/L与ADM 0.75μmol/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 16μmol/L、ADM 0.2μmol/L以及3-BrPA 16μmol/L与ADM0.2μmol/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 80μmol/L与ADM 0.75μmol/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(P<0.01);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。

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 320μ 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 p.mol/L） , adriamycin（0. 75,1.5,3,6,12 μmol/L） and 3-BrPA at 80 p, mol/L combined with adriamycin（0. 75,1.5, 3,6,12 μmol/L） for 24 h,48 h and 72 h in MDA-MB-231 breast cancer cells. Cells were treated with 3-BrPA（80 μ mol/L） , adriamyein（0.75 μmoL/L） and 3-BrPA（80 Ixmol/L） combined with adriamycin（0.75 μmol/L） for 24 hours,the apoptotic cells were detected using propidium iodide staining by flow cytometry. Cells were treated with 3-BrPA （ 16 μmol/L） , adriamycin （ 0.2 μmol/L） and 3-BrPA（ 16 μmol/L） combined with adriamycin （0. 5 μmol/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 eytotoxieity of ADM. When MDA-MB-231 breast cancer ceils were treated with 3-BrPA at 80 μmol/L combined with ADM at 0.75 μmol/L, the apoptosis rate was 39.6% ,which was significantly higher than that in control group,3-BrPA group and ADM group（P 〈0.01）. 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.