血清饥饿激活表皮生长因子受体诱导胃癌耐药

doi:10.3969/j.issn.1006-7795.2016.01.005

首都医科大学学报 ›› 2016, Vol. 37 ›› Issue (1): 23-29.doi: 10.3969/j.issn.1006-7795.2016.01.005

• 消化系统重大疾病的全链条研究 • 上一篇下一篇

血清饥饿激活表皮生长因子受体诱导胃癌耐药

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

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

收稿日期:2015-12-25 出版日期:2016-02-21 发布日期:2016-02-01
通讯作者: 郝建宇, 樊代明 E-mail:haojianyu@sina.com;daimingfan@fmmu.edu.cn
基金资助:
国家消化系统疾病临床医学研究中心基金(2015BAI13B09)。

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

Wang Junxiong^1,2,3,4,5, Cai Xiqiang¹, Nie Yongzhan¹, Hao Jianyu^3,4,5, Fan Daiming¹

1. Xijing Hospital of Digestive Diseases, Xijing Hospital, the Fourth Military Medical University, Xi'an 710032, China;
2 Medical and Health Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China;
3. Department of Gastroenterology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, China;
4. National Clinical Research Center for Digestive Diseases, Beijing 100050, China;
5. Faculty of Gastroenterology, Capital Medical University, Beijing 100050, China

Received:2015-12-25 Online:2016-02-21 Published:2016-02-01
Supported by:
This study was supported by the National Clinical Research Center for Digestive Diseases (2015BAI13B09).

摘要/Abstract

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。

关键词: 胃癌, 血清饥饿, 表皮生长因子受体, 耐药

Abstract: 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 MTT assay. The inhibition rates and IC50 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.

Key words: gastric cancer, serum starvation, epidermal growth factor receptor(EGFR), drug resistance

中图分类号:

R656.6

王俊雄, 蔡习强, 聂勇战, 郝建宇, 樊代明. 血清饥饿激活表皮生长因子受体诱导胃癌耐药[J]. 首都医科大学学报, 2016, 37(1): 23-29.

Wang Junxiong, Cai Xiqiang, Nie Yongzhan, Hao Jianyu, Fan Daiming. Serum starvation induces gastric carcinoma chemotherapy resistance through EGFR/ERK pathway[J]. Journal of Capital Medical University, 2016, 37(1): 23-29.

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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

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