厄贝沙坦联合表柔比星对乳腺癌细胞增殖的抑制作用及对survivin和VEGF表达的影响

Inhibition effect of irbesartan combined with epirubicin on proliferation of breast cancer cells and its influence on the expression of survivin and VEGF

目的研究厄贝沙坦联合表柔比星对MCF-7乳腺癌细胞增殖抑制作用及对生存素(survivin)和血管内皮生长因子(vascular endothelial growth factor,VEGF)表达的影响。方法采用MTT(噻唑蓝)法检测不同剂量表柔比星及厄贝沙坦联合表柔比星对乳腺癌MCF-7细胞分别作用24 h、48 h、72 h后的抑制率,用ELISA法(酶联免疫吸附法)检测空白对照组、表柔比星组(0.75μg/mL)、表柔比星联合厄贝沙坦组(0.75μg/mL+2.3μg/mL)、顺铂阳性对照组(5μg/mL)各组药物作用下细胞培养基中VEGF及survivin的表达水平。结果表柔比星对乳腺癌MCF-7细胞的半数抑制浓度(IC_(50))为0.75μg/mL,厄贝沙坦联合表柔比星对细胞增殖有显著抑制作用,且随着浓度的增加而增强,三个剂量组和空白对照组比较差异有统计学意义(P<0.05或0.01)。联合用药组与单用表柔比星组及阳性对照组分别作用24 h、48 h、72 h后与对照组比较VEGF的表达差异均无统计学意义(P>0.05)。表柔比星联合厄贝沙坦组中survivin表达水平与空白对照组相比差异有统计学意义(P<0.05),作用72 h后联合用药组与阳性对照组相比较,survivin的表达差异有统计学意义(P<0.01),联合用药组作用48 h、72 h和表柔比星组比较survivin的表达差异有统计学意义(P<0.01)。结论厄贝沙坦联合表柔比星对乳腺癌MCF-7细胞的增殖具有显著抑制作用,可以下调survivin的表达水平。

Objective To study the inhibition effect of irbesartan combined with epirubicin on proliferation of breast cancer cells and its influence on the expressions of survivin and vascular endothelial growth factor(VEGF).Methods MTT(Methylthiazolyldiphenyl-tetrazolium bromide)method was used to detect the inhibition rate of different dose of epirubicin and irbesartan combined with epirubicin on MCF-7 cells of breast cancer after action of drugs for 24 h,48 h and 72 h,respectively.ELISA(enzyme linked immunosorbent assay)was used to detect the expression levels of survivin and VEGF in cell culture medium under the action of drugs among blank control group,epirubicin group(0.75μg/mL),epirubicin combined with irbesartan group(0.75μg/mL+2.3μg/mL)and cisplatin positive control group(5μg/mL).Results The inhibitory concentration 50%(IC_(50))of epirubicin on MCF-7 cells of breast cancer was 0.75μg/mL,irbesartan combined with epirubicin had a significant inhibitory effect on cell proliferation,which increased with the increase of concentration,and difference between the three dose groups and the blank control group was statistically significant(P<0.05 or 0.01).After action of drugs for 24 h,48 h and 72 h,difference of VEGF expression levels between the epirubicin group,the cisplatin positive control group and the blank control group was not statistically significant(P>0.05).Difference of the expression levels of survivin between the epirubicin combined with irbesartan group and the blank control group was statistically significant(P<0.05).After action of drugs for 72 h,difference of the expression levels of survivin between the combined medication group and the blank control group was statistically significant(P<0.01).And action of drugs for 48 h and 72 h,difference of the expression levels of survivin between the combined medication group and the epirubicin group was statistically significant(P<0.01).Conclusion Irbesartan combined with epirubicin can significantly inhibit the proliferation of MCF-7 cells of breast cancer and down-regulate the expression level of survivin.