氯化锂对第10号染色体缺失的磷酸酶及张力蛋白同源基因缺失肿瘤的疗效分析  

Phosphatase and tensin homolog deleted on chromosome ten deficiency sensitizes tumor cells to lithium chloride treatment

作　　者：吴玉婷 马茜[2] 汤步富 刘芳铭 靳迪 王玲[4] 盖晓晨 张宏冰[1] Wu Yuting;Ma Qian;Tang Bufu;Liu Fangming;Jin Di;Wang Ling;Gai Xiaochen;Zhang Hongbing(Department of Physiology,Institute of Basic Medical Sciences and School of Basic Medicine,Peking Union Medical College and Chinese Academy of Medical Sciences,Beijing 100005,China;Institute of Cancer Stem Cell,Dalian Medical University,Dalian 116011,China;Department of Radiology,Second Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310000,China;Department of Oncology,First Affiliated Hospital,Dalian Medical University,Dalian 116011,China)

机构地区：[1]中国医学科学院北京协和医学院基础医学研究所生理系,北京100005 [2]大连医科大学肿瘤干细胞研究所,大连116011 [3]浙江大学医学院第二附属医院放射科,杭州310000 [4]大连医科大学第一附属医院肿瘤科,大连116011

出　　处：《中华医学杂志》2019年第30期2362-2366,共5页National Medical Journal of China

基　　金：中国医学科学院医学与健康科技创新工程重大协同创新项目(CAMS-2017-I2M-1-002).

摘　　要：目的探讨氯化锂(LiCl)对第10号染色体缺失的磷酸酶[丝氨酸蛋白激酶(GSK3)]及张力蛋白同源基因(PTEN)缺失肿瘤(子宫内膜癌)的疗效.方法首先,我们通过检索Catalogue ofSomatic Mutationsin Cancer数据库,分析人子宫内膜癌样本的基因突变谱.然后利用人子宫内膜癌细胞系和Pten^+/+、Pten^-/-小鼠胚胎成纤维细胞(MEF),分析PTEN蛋白丰度和细胞对LiC1敏感性之间的关系.研究观察LiC1对雷帕霉素靶蛋白(mTOR)信号通路的影响.以及LiC1对Pten缺失肿瘤的疗效.结果 39%的子宫内膜癌中发生PTEN突变.LiC1下调mTOR信号通路,优先抑制PTEN缺失人子宫内膜癌细胞和MEF的增殖,并且阻碍Pten缺失肿瘤的发展.结论 PTEN是子宫内膜癌中最常见的突变基因.通过靶向mTOR信号传导途径,LiC1对PTEN缺失细胞抑制作用更强,有望对治疗PTEN缺失肿瘤提供依据.Objective To identify the therapeutic efficacy of lithium chloride (LiCl) on phosphatase and tensin homolog deleted on chromosome ten (PTEN)-deficient tumors. Methods First, the Catalogue of Somatic Mutations in Cancer for mutation spectrum of human endometrial carcinoma samples was analyzed. Second, the relationship between PTEN abundance and LiCl inhibition of endometrial cancer cell lines using Pten^+/+ and Pten^-/- mouse embryonic fibroblast (MEF) lines was investigated. Moreover, potential alterations of mammalian target of rapamycin (mTOR) signaling pathway after treatment with LiCl were checked.Last,LiCl′s efficacy on PTEN null tumors was studied. Results PTEN was mutated in 39% of endometrial carcinomas. LiCl preferentially inhibited the proliferation of PTEN-deficient endometrial carcinoma cells and MEFs. Furthermore, LiCl blocked PTEN-deficient tumor development. Mechanistically, LiCl down-regulated mTOR signaling. Conclusions PTEN is the most frequently mutated gene in endometrial carcinoma.By targeting mTOR signaling pathway,LiCl is a promising regimen for the treatment of tumors with PTEN deficiency.

关 键 词：子宫内膜癌 氯化锂 丝氨酸蛋白激酶 雷帕霉素靶蛋白 基因 

分 类 号：R737.33[医药卫生—肿瘤]