IDH1基因在非小细胞肺癌化疗耐受中的作用  

The effect of IDH1 on chemotherapy tolerance in non-small cell lung carcinoma

作　　者：许俊[1] 邓远[1] 范国华 倪正义 周密[1] 许海 XU Jun DENG Yuan FAN Guo-hua NI Zheng-yi ZHOU Mi XU Hai(Department of Surgery, the Center of Medical Treatment, Wuhan, Hubei 430023 Department of Surgery, Hubei Provincial People＇s Hospital, Wuhan, Hubei 430023 Huangfiahu Hospital of Hubei Traditional Chinese Medicine University, Wuhan , Hubei 430060, China)

机构地区：[1]武汉市医疗救治中心外科,湖北武汉430023 [2]湖北省人民医院外科,湖北武汉430023 [3]湖北中医药大学黄家湖医院妇科,湖北武汉430060

出　　处：《热带医学杂志》2017年第9期1148-1151,F0003,共5页Journal of Tropical Medicine

基　　金：中国博士后科学基金(2013M542498)

摘　　要：目的探讨异柠檬酸脱氢酶1(IDH1)在人非小细胞肺癌化疗耐受中的作用及可能机制。方法免疫组织化学和Western blot检测人正常肺组织、未经化疗和多次化疗的非小细胞肺癌组织中IDH1的蛋白表达;构建稳定下调IDH1表达的肺癌细胞株A549,MTT法检测该细胞对化疗药物顺铂和紫杉醇的敏感性。结果在经多次化疗的非小细胞肺癌患者中,免疫组化和Western blot结果显示IDH1蛋白的表达水平明显高于未经化疗的非小细胞肺癌患者和正常对照人群,三组阳性率比较,差异有统计学意义(P<0.05)。利用sh RNA构建稳定下调IDH1的细胞株,MTT显示A549细胞中下调IDH1表达后,顺铂和紫杉醇对其抑制能力增强,使得细胞对顺铂和紫杉醇敏感性升高。结论 IDH1在非小细胞肺癌对化疗药物的敏感性中起重要作用,其高表达可能导致肺癌对化疗耐受及差预后。Objective To study the role of isocitrate dehydrogenases 1（IDH1）in human non-small cell lung carcinoma chemotherapy tolerance and its possible mechanisms. Methods Immunohistochemistry and western blot was performed to detect the expression of IDH1 protein in human normal lung,non-small cell lung carcinoma without chemotherapy,and nonsmall cell lung carcinoma with multiple chemotherapy. The A549 cell line in which the IDH1 was stably knocked down was constructed. Then,MTT was used to detect the sensitivity of cisplatin and paclitaxel on A549 cell at the different level of IDH1 protein. Results IHC and western blot results showed that the protein expression of IDH1 in non-small cell lung carcinoma patients with repeated chemotherapy was significantly higher than in patients without chemotherapy and normal subjects. The positive rate of the three groups was compared,and the difference was statistically significant（P〈0.05）. A549 cells with stable down regulation of IDH1 were constructed by sh RNA. The inhibition of cisplatin and paclitaxel on A549 cell increased after IDH1 was knocked down,indicating that IDH1 down regulation increased the sensitivity of A549 cells to cisplatin and paclitaxel. Conclusion IDH1 plays an important role in non-small cell lung cancer cell sensitive to chemotherapeutic drugs. High expression of IDH1 in lung cancer may lead to chemotherapy tolerance and poor prognosis of lung cancer.

关 键 词：异柠檬酸脱氢酶1 非小细胞肺癌 化疗 耐受 

分 类 号：R734.2[医药卫生—肿瘤]