曲妥珠单抗对HER-2过表达乳腺癌细胞株mTOR信号通路影响的观察  

Effect of Trastuzumab on the mTOR signaling in the HER-2-overexpressing breast cancer cell

作　　者：郭婧昀[1] 姚广裕[1] 顾繁[1] 陈路嘉[1] 陈睿婷[1] 李文姬[1] 叶长生[1] 

机构地区：[1]南方医科大学附属南方医院乳腺科,广东广州510515

出　　处：《中华肿瘤防治杂志》2012年第13期983-986,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：广东省科技计划项目(2003C34206)

摘　　要：目的:探讨曲妥珠单抗对HER-2过表达乳腺癌细胞株mTOR信号通路的影响。方法:在培养的乳腺癌细胞株MDA-MB-453中加入曲妥珠单抗,采用蛋白质印迹法检测细胞中mTOR、S6、4EBP1和Akt的蛋白磷酸化水平,同时检测该药对MDA-MB-453增殖及克隆形成的影响。结果:乳腺癌细胞株MDA-MB-453在加入曲妥珠单抗作用下,mTOR、S6、4EBP1和Akt磷酸化明显受抑制,并具有浓度依赖性;乳腺癌细胞株MDA-MB-453在加入曲妥珠单抗后,细胞相对增殖率随着药物浓度增大由(77±6.3)%降至(21±1.5)%,克隆形成率随着药物浓度增大由(55±4)%降至(4±1)%。结论:曲妥珠单抗可通过抑制mTORC1和mTORC2信号通路,从而抑制乳腺癌细胞株MDA-MB-453的生长与增殖。OBJECTIVE： To study the effect of Trastuzumab on the roTOR signaling in the HER-2-overexpressing breast cancer cell（MDA-MB-453）. METHODS： The HER-2-overexpressing breast cancer cell （MDA-MB-453） was estab- lished. The Trastuzumab stimulation was then added in the cells. The expression of mTOR,S6,4EBP1, Akt and its phos- phorylation proteins were detected by western blot ananlysis. The proliferation assay and clone formation assay have been conducted. RESULTS： The phosphorylation of mTOR, S6,4EBP1, Akt were inhibited by Trastuzumab in a dose-depend- ent manner in the HER-2-overexpressing breast cancer cell（MDA-MB-453）. The ralative proliferation rate was decreased from （77±6.3）% to （21±1.5）% with the increasing concentrations. Respectively,the clone formation rate has been re- duced significantly from （55 ±4） % to （4±1 ） %. CONCLUSION ： Trastuzumab, targating for HER 2 protein, could inhibit both mTORC1 and mTORC2 signaling pathway to benefit the proliferation inhibition effects.

关 键 词：曲妥珠单抗 MTOR 乳腺肿瘤 HER-2 

分 类 号：R737.9[医药卫生—肿瘤]