蛋白酶体抑制剂MG132联合3种化疗药物增强对人乳腺癌细胞的抑制作用

Enhanced inhibitory effects on human breast cancer cells by proteasome inhibitor MG132 added to a triple-drug chemotherapy

目的：观察蛋白酶体抑制剂MG132联合使用3种化疗药物对人乳腺癌细胞MCF-7的抑制作用。方法：采用Alamar Blue^TM方法检测细胞的生长抑制效应。实验分4组：①化疗药物处理组（紫杉醇、紫苹素或阿霉素的不同浓度）；②MG132组（1．25、2．5、5、10μmoL／L）；③MG132联合3种化疗药物处理组；④溶剂对照组。MCF-7细胞分别使用上述药物处理40h后，加入Alamar Blue^TM孵育8h，测定OD值并计算细胞相对活力。结果：①MG1325μLmol／L及其以下浓度对MCF－7没有抑制效应；②3种化疗药物的不同浓度处理细胞后，细胞活力随药物的浓度升高明显下降，具有明显的剂量依赖效应；③选择MG1325μmol／L分别与3种化疗药物联合处理后，MCF－7细胞的活力明显下降，紫杉醇为19．10％、紫苹素19．13％，阿霉素27．17％，与化疗药物处理组比较差异有统计学意义（P〈0．05）。结论：蛋白酶体抑制剂MG132明显增强紫杉醇、紫草素和阿霉素对MCF-7细胞的抑制作用。

Objective：To observe the inhibitory effects on human breast cancer cells （MCF-7） by proteasome inhibitor MG132 added to a triple-drug chemotherapy. Methods： AlamarBlueTM assay was used to detect the cell viability. MCF-7 cells ware randomly divided into four groups ： chemotherapeutics treated group （ several concentrations of paclitaxel,shikonin or doxorubicin） , MGI32 treated group （ 1.25μmol/L,2.5μmol/L,5μmol/L and lOp.tool/L）, MG132 plus chemotherapeuties group and solvent control group. After MCF-7 cells were treated for 40hrs, AlamarBlue^TM was added for 8 hours and the OD value was detected to calculate the relative viability of cells. Results： ①There was no significant inhibitory effect when MCF-7 cells were treated with MG132 at doses not higher than 5 μmol/L; ② Relative cell viability decreased significantly with increasing doses of 3 chemotherapeutics in an apparent dose-dependant manner;③Afier MCF-7 cells were concurrently treated with 5 μmol/L MG132 and chemotherapeutics, the relative cell viability was reduced dramatically （to 19.10% with paclitaxel, 19.13% with shikonin, and 27.17% with doxorubicin） ,compared with single use of chemotherapeutics （P 〈 0.05 ）. Conclusion： The inhibitory effect of paclitaxel, shikonin and doxorubiein on MCF-7 cells was enhanced significantly by proteasome inhibitor MG132.