谷胱甘肽过氧化物酶-1与人子宫内膜癌顺铂抵抗的关系及相关机制研究  

Relationship between glutathione peroxidase-1 and cisplatin resistance in human endometrial carcinoma cells and its related mechanism

作　　者：许林芬[1] 赵荣[1] 方美仙 付丽东 林明英[1] 林美双[1] 李佳凤[3] XU Lin-fen;ZHAO Rong;FANG Mei-xian;FU Li-dong;LIN Ming-ying;LIN Mei-shuang;LI Jia-feng(Department of Gynecology, Maternal and Child Health Hospital of Fujian Province, Affiliated Hospital of Fufian Medical University, Fuzhou 350004, China;Department of Gynecology, Nanping First Hospital AJ~liated to Fujian Medical University, Nangping 353000, Fujian Province, China;Department of Pharmacy, Maternal and Child Health Hospital of Fujian Province, Affiliated Hospital of Fujian Medical University, Fuzhou 350004, China)

机构地区：[1]福建省妇幼保健院福建医科大学附属医院妇科,福州350004 [2]福建医科大学附属南平市第一医院妇科,福建南平353000 [3]福建省妇幼保健院福建医科大学附属医院药剂科,福州350004

出　　处：《中国临床药理学杂志》2018年第8期953-956,共4页The Chinese Journal of Clinical Pharmacology

基　　金：吴阶平医学基金会临床科研基金资金项目(2011-427-2039)

摘　　要：目的研究谷胱甘肽过氧化物酶-1(GPX1)对子宫内膜癌细胞顺铂抵抗的影响及相关机制。方法用顺铂间歇浓度梯度递增法制备顺铂抵抗HEC-1-A CR细胞,以等量0.9%Na Cl制备对照HEC-1-A细胞;慢病毒转染过表达载体上调HEC-1-A CR的GPX1表达来制备HEC-1-A CR GPX1细胞,转染空白载体作为HEC-1-A CR对照细胞。以溴化噻唑蓝(MTS)比色法检测细胞顺铂半抑制浓度(IC_(50))值,以荧光定量链式聚合酶反应和蛋白免疫印迹法检测细胞GPX1及HIF-1α的mRNA与蛋白表达。结果 HEC-1-A细胞株与HEC-1-A CR细胞株顺铂的IC50值分别为(2.13±0.24),(7.89±1.17)μg·m L^(-1);HEC-1-A CR对照细胞株与HEC-1-A CR GPX1细胞株顺铂的IC50值分别为(7.91±0.98),(3.87±0.52)μg·m L^(-1)。HEC-1-A细胞株与HEC-1-A CR细胞株的GPX1 mRNA表达量分别为0.14±0.01,0.07±0.01;这2个细胞株的HIF-1αmRNA表达量分别为0.32±0.03,0.72±0.08。HEC-1-A CR对照细胞株与HEC-1-A CR GPX1细胞株GPX1的mRNA表达量分别为0.09±0.02,0.24±0.03;这2个细胞株的HIF-1αmRNA表达量分别为0.76±0.08,0.54±0.05,上述指标在组间比较,差异均有统计学意义(均P<0.05)。GPX1及HIF-1α蛋白水平变化与mRNA水平变化一致。结论 GPX1通过下调HIF-1α的表达,可以促进子宫内膜癌细胞对顺铂敏感性的增强。Objective To investigate the effect of glutathione peroxidase-1（ GPX1） on cispatin resistance in endometrial carcinoma cells and its related mechanism. Methods The HEC-1-A cisplatin resistance（ HEC-1-A CR） cell was constructed by intermittent concentration gradient method. The control HEC-1-A cell was constructed with equal amount of normal saline. Lentivirus transfection was used to up-regulate the expression of GPX1 in the HEC-1-A CR cell as HEC-1-A CR GPX1 cell,and blank vector transfected was regarded as HEC-1-A CR control cell. The half maximal inhibitory concentration（ IC（50）） value of cisplatin in cells was detected by thiazolyl blue（ MTS） assay. The expression of mRNA and protein of GPX1 and HIF-1α were detected by fluorescent quantitative chain reaction（ q PCR） and Western blotting.Results The IC50 of HEC-1-A cells and HEC-1-A CR cells were（ 2. 13 ± 0. 24）,（ 7. 89 ± 1. 17） μg·m L-（-1）. The IC50 of HEC-1-A CR control cells and HEC-1-A CR GPX1 cells were（ 7. 91 ± 0. 98）,（ 3. 87 ± 0. 52） μg · m L-（-1）. The expression level of GPX1 mRNA in HEC-1-A cells and HEC-1-A CR cells were 0. 14 ± 0. 01,0. 07 ± 0. 01. The expression level of HIF-1α mRNA in HEC-1-A cells and HEC-1-A CR cells were 0. 32 ± 0. 03,0. 72 ± 0. 08. The expression level of GPX1 mRNA in HEC-1-A CR control cells and HEC-1-A CR cells were 0. 09 ± 0. 02,0. 24 ± 0. 03. The expression level of HIF-1α mRNA in HEC-1-A CR control cells and HEC-1-A CR cells were 0. 76 ± 0. 08,0. 54 ± 0. 05. The above indexes were compared between groups,the difference was statistically significant（ all P〈0. 05）. The results of the changes of GPX1 and HIF-1α protein levels were in accordance with the changes of mRNA levels. Conclusion GPX1 can enhance the sensitivity of cisplatin in endometrial cancer cells via down-regulating the expression of HIF-1α.

关 键 词：子宫内膜癌 谷胱甘肽过氧化物酶-1 缺氧诱导因子-1Α 化疗抵抗 

分 类 号：R737.33[医药卫生—肿瘤]