血清饥饿激活表皮生长因子受体诱导胃癌耐药  

Serum starvation induces gastric carcinoma chemotherapy resistance through EGFR/ERK pathway

作　　者：王俊雄[1,2,3,4,5] 蔡习强[1] 聂勇战[1] 郝建宇[3,4,5] 樊代明[1] 

机构地区：[1]第四军医大学西京消化病医院,西安710032 [2]首都医科大学附属北京友谊医院医疗保健中心,北京100050 [3]首都医科大学附属北京朝阳医院消化内科,北京100431 [4]国家消化系统疾病临床医学研究中心,北京100050 [5]首都医科大学消化病学系,北京100050

出　　处：《首都医科大学学报》2016年第1期23-29,共7页Journal of Capital Medical University

基　　金：国家自然科学基金(81120108005;81172096);国家消化系统疾病临床医学研究中心基金(2015BAI13B09)~~

摘　　要：目的探讨血清饥饿对表皮生长因子受体(epidermal growth factor receptor,EGFR)高表达胃癌细胞化学药物治疗(以下简称化疗)敏感性的影响及其作用机制。方法将胃癌细胞分为4组:正常对照组、饥饿组、化疗药处理组、饥饿+化疗药处理组。采用噻唑蓝[3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide,MTT]方法观察肿瘤细胞的存活率,两两比较验证血清饥饿对化疗药敏感性的影响。采用Western blotting法观察细胞EGFR及其下游靶分子细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK),蛋白激酶B(RAC-alpha serine/threonine-protein kinase,Akt)的磷酸化水平变化;最后进一步借助EGFR单克隆抗体西妥昔单抗抑制EGFR的磷酸化的活性,观察其对胃癌细胞化疗感性的影响。结果与对照组相比,胃癌细胞SGC7901血清饥饿时对多种化疗药物的敏感性下降,血清饥饿可促进EGFR、ERK磷酸化,差异有统计学意义(P<0.05)。EGFR单克隆抗体可部分逆转血清饥饿所导致的化疗药耐药。结论缺营养饥饿可诱导EGFR高表达胃癌细胞化疗耐药,其诱导机制可能与激活EGFR/ERK信号通路有关。Objective To demonstrate drug resistance induced by serum starvation in gastric cancer and explore the possible mechanism. Methods The viability of SGC7901 cells was measured by MTY assay. The inhibition rates and ICS0 values were then calculated. The phosphorylation level of EGFR and ERK induced by serum starvation were measured by Western blotting. Results Serum starvation could reduce the action of chemotherapeutic drug. EGFR signal activation acted as a protective factor against starvation by regulating downstream genes. Compared with the control group, the phosphorylation levels of EGFR and ERK were significantly increased in serum starvation treatment group （P 〈 0. 05）. EGFR monoclonal antibody could partially reverse multiple drug resistance as a result of serum starvation. Conclusion Serum starvation may induce drug resistance in gastric cancer cell and the mechanism may be related to the activation of EGFR/ERK signaling pathway.

关 键 词：胃癌 血清饥饿 表皮生长因子受体 耐药 

分 类 号：R656.6[医药卫生—外科学]