曲妥珠单抗对不同pH培养HER2阳性乳腺癌细胞增殖的抑制及促凋亡作用  

Effect of Trastuzumab on Proliferation and Apoptosis of HER2 Breast Cancer Cell with Different pH Culture

作　　者：段巧虹[1] 张腾跃[1] 黄海良[2] 刘亚贝[1] 马克龙[3] 范平生[1] 荚卫东[4] 

机构地区：[1]安徽省肿瘤医院肿瘤内二科,合肥230031 [2]安徽医科大学生化与分子生物学教研室,合肥230032 [3]安徽中医学院表观遗传学实验室,合肥230038 [4]安徽省立医院肝脏外科,合肥230001

出　　处：《微循环学杂志》2013年第4期1-3,7,F0002,I0001,共6页Chinese Journal of Microcirculation

基　　金：国家自然科学基金(No:81172364);安徽省科技厅年度计划项目(12070403058)

摘　　要：肿瘤细胞外酸性微环境是肿瘤形成和进展的关键环节，亦是导致肿瘤细胞对放疗和化疗药物不敏感的原因之一。乳腺癌除了手术和放疗外，化学药物治疗也是临床重要手段（根据细胞膜靶蛋白的表达特点制定相应的治疗措施）。但由于肿瘤细胞内外环境，尤其是酸性环境导致的分子功能的变异，使得药物治疗效果并不理想，复发率较高。因此，寻找药物治疗的适宜pH环境成为当务之急。Objective:To observe the effect of trastuzumab on proliferation and apoptosis of breast cancer cell SKBR3 with different pH value culture. Method:Using different pH(6.4,6.8,7.2,7.4,7.6)medium,culturing SKBR3cells,10ug/ml trastuzumab was chosen as the experimental drug concentration.MTT method was used to detect the proliferation of cells with different pH values under the trastuzumab action;the cells apoptosis rate of trastuzumab was detected by tunnel method;expression of breast cancer cell signaling proteins(Bcl-2,NF-κB,pAKT)were detected by western blotting method.Results:With the increase of pH value of medium,the inhibitory effect of trastuzumab on breast cancer cell proliferation and apoptosis was increased.If cells cultured in pH7.4 or 7.6, proliferation of cells was significantly lower than the pH values of 6.4~ 7.2(P<0.05),and apoptosis rate was significantly higher(P<0.05). Along with the pH value increased,the expression of signaling protein changes as:the lower expression of pAKT,NF-κB,Bcl-2anti-apoptosis proteins was detected(P<0.05).Conclusion:Trastuzumab has inhibitory effect on proliferation and promotion effect on apoptosis of breast cancer cells with higher pH,which provides experimental basis for clinical antitumor treatment accompaning with alkalization.

关 键 词：pH环境 乳腺癌 促凋亡作用 癌细胞增殖 曲妥珠单抗 HER2 化学药物治疗 阳性 

分 类 号：R73-361[医药卫生—肿瘤] R737.9[医药卫生—临床医学]