抑癌基因高甲基化与胃癌化疗药物敏感相关性的探讨  

Correlation between suppressor genes promoter hypermethylation and chemosensitivity of gastric cancer

作　　者：林海[1] 曹俊[2] 戴伟杰[1] 邹晓平[1] 

机构地区：[1]南京医科大学鼓楼临床医学院消化内科,江苏南京210008 [2]南京大学医学院附属鼓楼医院消化内科,江苏南京210008

出　　处：《中华肿瘤防治杂志》2011年第9期688-692,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：江苏省卫生厅医学重点人才资助项目(RC2007003)

摘　　要：目的:研究抑癌基因p16、MG-MT、DAPK启动子甲基化与胃癌患者临床病理参数及对化疗药物敏感性的关系。方法:MSP检测38例胃癌组织及相应20例正常胃黏膜组织p16、MGMT、DAPK基因启动子甲基化状况。MTT法检测5-氟尿嘧啶(5-FU)、顺铂(DDP)、多柔比星(ADM)、吉西他滨(GEM)、丝裂霉素(MMC)等化疗药物单用及联用对38例原代胃癌细胞的抑制率。并比较p16、MGMT、DAPK甲基化与非甲基化组胃癌对化疗药物的敏感性差异。结果:三基因在胃癌组织中甲基化率均明显高于正常胃黏膜组织,P<0.05。p16甲基化与Lauren分型相关,DAPK甲基化与胃癌TNM分期相关,P值均<0.05。p16甲基化组5-FU、5-FU+DDP+ADM及5-FU+DDP+GEM抑制率高于非甲基化组;DAPK甲基化组MMC抑制率低于非甲基化组,P值均<0.05。结论:抑癌基因启动子高甲基化可能是胃癌发生发展过程中的重要事件。不同抑癌基因发生甲基化对胃癌化疗敏感性影响可能不同。OBJECTIVE： To explore the relationship between suppressor genes p16, MGMT,DAPK promoter methylation and clinicopathological parameters of patients with gastric cancer and the sensitivity to chemotherapeutic drugs. METHODS： Fresh tissues from 38 pathologically diagnosed gastric carcinoma patients and normal tissues （n=20） were collected. The methylation-specific PCR was used to detect the promoter methylation of pl6,MGMT,DAPK. The chemosensitivity of chemotherapeutic drugs （5-FU, DDP, ADM, GEM, MMC）, combined administration or sole-administration, to gastric cancer cell lines from the tissues was tested by MTT assay and the chemosensitivity difference of the methylated group was compared with that of the unmethylated group to the chemotherapy drugs. RESULTS： The rates of methylation of p16, MGMT and DAPK were higher than those in corresponding normal tissues （P〈0. 05）. The p16 metbylation rates in intestinal type were higher than those in diffuse type gastric cancer, and DAPK methylation was associated with TNM stage （P〈 0.05）. p16 methylation was associated with a higher chemosensitivity to 5-FU, 5-FU＋DDP＋ADM and 5-FU＋DDP＋GEM. DAPK methylation was associated with a lower chemosensitivity to MMC （P〈0. 05）. CONCLUSIONS： Promoter hypermethylation of tumor suppressor gene may be major events in the development of gastric carcinoma. Different suppressor genes promoter methylation perhaps has different impact on the chemosensitivity of gastric cancer.

关 键 词：胃肿瘤/药物疗法 DNA甲基化 抗药性 肿瘤 

分 类 号：R735.2[医药卫生—肿瘤]