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.
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 of Somatic 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LiCl敏感性之间的关系。研究观察LiCl对雷帕霉素靶蛋白（mTOR）信号通路的影响。以及LiCl对Pten缺失肿瘤的疗效。 结果： 39%的子宫内膜癌中发生PTEN突变。LiCl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，LiCl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。.
Keywords: Endometrial carcinoma; GSK3; Gene; LiCl; mTOR.