PTEN Deficient Tumor Treatment With Lithium Chloride

Objective:To check the efficacy of Lithium Chloride(LiCl)on PTEN deficient tumor.Method:First,we analyzed the Catalogue of Somatic Mutations in Cancer for mutation spectrum of human endometrial carcinoma samples.Second,we studied the relationship between PTEN abundance and LiCl's sensitivity of endometrial cancer cell lines and Pten+/+ and Pten-/-mouse embryonic fibroblasts(MEFs).Third,we checked potential alterations of mTOR signaling pathway by LiCl.Last,we investigated Lil's efficacy on Pten null tumors.Results:PTEN is mutated in 39%endometrial carcinomas.PTEN deficiency sensitizes endometrial carcinoma cells and MEFs to LiCl treatment.Furthermore,LiCl blocked Pten null tumor development.Mechanistically,the anti-proliferation effect of LiCl is mTOR dependent but irrelevant of GSK3?.Conclusions:PTEN is the most frequently mutated gene in endometrial carcinoma.By targeting mTOR signaling pathway,LiCl is a promising therapeutic regimen for tumors with PTEN deficiency.