Shikonin suppresses proliferation and induces apoptosis in endometrioid endometrial cancer cells via modulating miR-106b/PTEN/AKT/mTOR signaling pathway.
Biosci Rep. 2018 Feb 15. Epub 2018 Feb 15. PMID: 29449346
Shikonin, a natural naphthoquinone isolated from a traditional Chinese medicinal herb, which exerts anti-cancer effects in various cancers. However, the molecular mechanisms underlying the therapeutic effects of shikonin against endometrioid endometrial cancer (EEC) have not yet been fully elucidated. Herein, we investigated anti-cancer effects of shikonin on EEC cells and explored the underlying molecular mechanism. We observed that shikonin inhibits proliferation in human EEC cell lines with in a dose-dependent manner. Moreover, shikonin-induced apoptosis was characterized by the upregulation of the pro-apoptotic proteins cleaved-Caspase-3 and Bax, and the downregulation of the anti-apoptotic protein Bcl-2. Microarray analyses demonstrated that shikonin induces many miRNAs dysregulation, and the miR-106b was one of the miRNAs being most significantly downregulated. miR-106b was identified to exert pro-cancer effect in various cancers, but in EEC remains unclear. We firstly confirmed that miR-106b is upregulated in EEC tissues and cells, and knockdown of miR-106b suppresses proliferation and promotes apoptosis. Meanwhile, our results validated that the restored expression of miR-106b abrogates the anti-proliferative and pro-apoptotic effects of shikonin. We also identified that miR-106b targets PTEN, a tumor suppressor gene, which in turn modulates AKT/mTOR signaling pathway. Our findings indicated that shikonin inhibits proliferation and promotes apoptosis in human EEC cells by modulating the miR-106b/PTEN/AKT/mTOR signaling pathway, suggesting shikonin could act a potential therapeutic agent in the EEC treatment.