JNK信号通路介导ghrelin对乳腺癌MDA-MB-231细胞耐药蛋白表达的影响  

Ghrelin enhances expression of P-glycoprotein in breast cancer MDA-MB-231 cells through JNK signaling pathway

作　　者：曲文志[1] 杨蕾[1] 张云微 金光华[1] 李子豪[1] 涂巍[1] 

机构地区：[1]中国医科大学附属第四医院第五普通外科,辽宁沈阳110032

出　　处：《实用肿瘤杂志》2016年第4期340-344,共5页Journal of Practical Oncology

基　　金：辽宁省科学技术计划项目(2013225303)

摘　　要：目的探讨ghrelin调控c-Jun氨基末端激酶(c-Jun N-terminal kinase,JNK)信号转导通路对乳腺癌细胞P-糖蛋白表达的影响。方法培养人乳腺癌MDA-MB-231细胞,分别加入生长激素释放肽(ghrelin,100 nmol/L,干预72小时)、多柔比星(0.8 mg/L,干预72小时)、ghrelin联合多柔比星(ghrelin 100 nmol/L,多柔比星0.8 mg/L,干预72小时)。采用MTT方法检测细胞增殖,Western blot法检测细胞JNK、P-糖蛋白(P-glycoprotein,P-gp)的表达及p-JNK水平。结果 MTT检测显示,人乳腺癌MDA-MB-231细胞在ghrelin的干预下增殖(P<0.01),存活率在多柔比星的干预下降低(P<0.01),ghrelin联合多柔比星能够抑制多柔比星对MDA-MB-231细胞的杀伤作用(P<0.01)。ghrelin组JNK表达及p-JNK水平上升(均P<0.01),且P-gp蛋白表达上升(P<0.05);多柔比星组JNK表达及p-JNK水平下降(均P<0.01);ghrelin联合多柔比星较多柔比星组JNK表达及p-JNK水平增加,且P-gp表达明显上升(均P<0.05)。结论 ghrelin激活JNK信号通路干预乳腺癌细胞P-gp表达增加从而抑制多柔比星诱导乳腺癌细胞凋亡。Objective To investigate the effect of ghrelin on the expression of P-glycoprotein（ P-gp） in breast cancer cells and its mechanism. Methods Human breast cancer MDA-MB-231 cells were cultured with 100 nmol / L ghrelin for72 h,0. 8 mg / L doxorubicin for 72 h or 100 nmol / L ghrelin combined with 0. 8 mg / L doxorubicin for 72 h,respectively.MTT method was used to detect cell proliferation. The protein levels of JNK,P-gp and p-JNK were analyzed by Western blot. Results MTT assay showed that the proliferation of MDA-MB-231 cells was increased with ghrelin treatment（ P〈0. 01）; the cell survival rate was significantly decreased after doxorubicin treatment（ P〈0. 01）. Ghrelin combined with doxorubicin inhibited the effect of doxorubicin on MDA-MB-231 cells（ P〈0. 01）. The expression of JNK and p-JNK in ghrelin treated cells was increased significantly（ P〈0. 01）,while that in doxorubicin treated cells was decreased（ P〈0. 01）. In cells treated with both ghrelin and doxorubicin,the expression of JNK and p-JNK was higher than that in doxorubicin group,and P-gp expression was also significantly increased（ P〈 0. 05）. Conclusion Ghrelin activates JNK signaling pathway to induce the expression of P-gp in breast cancer cells,which subsequently inhibits doxorubicin mediated apoptosis of breast cancer cells.

关 键 词：乳腺肿瘤/病理学 JNK丝裂原活化蛋白激酶类 信号传导 髓磷脂P0蛋白质 肿瘤蛋白质类 P糖蛋白 多柔比星 

分 类 号：R737.9[医药卫生—肿瘤] R730.23[医药卫生—临床医学]