德氮吡格影响人肝癌细胞株QGY-7701亚细胞的蛋白质组学研究  

Subcelinlar proteomic analysis of Tetrazanbigen on human hepatocellular carcinoma cell line QGY-7701

作　　者：袁拥华[1] 杨晓兰[2] 李伟 郑小红[2] 谷容[1] 余瑜[2] 

机构地区：[1]重庆医科大学儿童发育疾病研究省部共建教育部重点实验室,400014 [2]重庆医科大学药学院药物化学教研室、重庆高校药物工程研究中心

出　　处：《中华肝脏病杂志》2011年第12期908-911,共4页Chinese Journal of Hepatology

基　　金：基金项目：国家自然科学基金（30772595）

摘　　要：目的观察德氮吡格（TNBG）对人肝癌细胞QGY-7701亚细胞蛋白表达的影响，探讨其影响脂代谢的分子机制。方法分别提取TNBG处理前后人肝癌细胞QGY-7701的细胞质、细胞膜和细胞核蛋白进行双向电泳，PDQuest7．4．0软件分析比对图像，采用基质辅助激光解吸电离飞行时间质谱技术（MALDI—TOF-MS）鉴定差异蛋白质点。结果TNBG作用于人肝癌细胞QGY-770172h后，细胞质的差异表达蛋白质点有56个，细胞膜的差异表达蛋白质点有65个，细胞核的差异表达蛋白质点有34个，共计155个。利用MALDI—TOF-MS技术鉴定出其中33个差异表达蛋白质点，其中包括与脂质合成有关的10个蛋白质点和与脂质降解、转运有关的7个蛋白质点，如3-羟基-3甲基戊二酸单酰辅酶A还原酶、角鲨烯合成酶、低密度脂蛋白受体、三磷酸腺柠檬酸裂解酶、甘油醛-3-磷酸脱氢酶、甘油-3-磷酸酰基转移酶、长链酯辅酶A脱氢酶等，这些都是固醇调节元件结合蛋白调控的靶基因。结论TNBG可能通过固醇调节元件结合蛋白途径增加胆固醇和甘油三酯合成，导致肿瘤细胞内脂滴大量聚积。Objective To investigate the clinical efficacy of cryotherapy ablation treatment for advanced hepatocellular carcinoma, and to analyse the predictive factors ofcryotherapy ablation treatment. Methods 190 patients of hepatitis B-related advanced HCC from 2005 to 2008 in our hospital underwent curative cryoablation. We used clinical cohort method to analyze cryoablation group （147 cases） and control group （43 cases）. The median OS （over survival time） and TTP （time to disease progression） were compared. We also evaluated the clinical significance of age, gender, location of portal vein tumor thrombus, HBeAg, tumor histological grade, Child-Pugh classification, end-stage liver disease （MELD） score, advanced liver cancer prediction system （ALCPS） score and the Eastern Cooperative Oncology Group performance status （ECOG PS） score for predicting the efficacy of cryoablation. Two Groups were compared with the x2 test. Survival rates were estimated by the Kaplan-Meier method and compared by the log rank test. The Cox proportional hazards model was used to determine the independent factors on survival based on the variables selected in univariate analysis. Results Median survival time of cryoablation goup and Control group were 7.5 （4.2 to 14.6） months and 3.2 （1.2 to 8.6） months, median TTP were 3.5 （2.5 to 4.5） months and 1.5 （1.0 to 3.5 months）, the differences between were statistically significant （P〈 0.05）. Median OS and TTP of advanced HCC patients who had Well-differentiated tumor, Child-pugh A-class and low score of MELD score, ALCPS score; ECOG PS score were significantly longer than that of the poorly differentiated tumor, Child-pugh B-class and the high those scores （P〈 0.05）. ECOG PS （P〈0.05, 95% CI 1.074 -2.143） and ALCPS （P〈0.05, 95% CI 1.005-2.121） were independent predictors for OS of advanced HCC. Conclusions Cryoablation treatment can prolong median OS and TTP of advanced HCC. ECOG PS and ALCPS are important predictors for survival time

关 键 词：癌 肝细胞 蛋白质组学 脂代谢障碍 德氮吡格 

分 类 号：R735.7[医药卫生—肿瘤]