Cryptotanshinone induces cell cycle arrest and apoptosis through the JAK2/STAT3 and PI3K/Akt/NFkB pathways in cholangiocarcinoma cells

• DOI: 10.2147/dddt.s132488
• Publication Date: 2017-06-16T03:05:07Z
• Authors: Fayong Ke; Zheng Wang; Xiaoling Song; Qiang Ma; Yunping Hu; Lin Jiang; Yijian Zhang; Yingbin Liu; Yong Zhang; Wei Gong
• Keywords: Propidium iodide

Cholangiocarcinoma (CCA) is the most common biliary tract malignancy in world with high resistance to current chemotherapies and extremely poor prognosis. The main objective of this study was investigate inhibitory effects cryptotanshinone (CTS), a natural compound isolated from Salvia miltiorrhiza Bunge, on CCA both vitro vivo explore underlying mechanisms CTS-induced apoptosis cell cycle arrest.The anti-tumor activity CTS HCCC-9810 RBE cells assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay colony forming assays. Cell changes were detected flow cytometric analysis. Apoptosis annexin V/propidium iodide double staining Hoechst 33342 efficacy evaluated using xenograft model athymic nude mice. expression key proteins involved signaling pathway analyzed Western blot analysis.CTS induced potent growth inhibition, S-phase arrest, apoptosis, colony-forming inhibition dose-dependent manner. Intraperitoneal injection (0, 10, or 25 mg/kg) for 4 weeks significantly inhibited xenografts treatment arrest decrease cyclin A1 an increase D1 protein level. Bcl-2 downregulated remarkably, while Bax increased after occurred. Additionally, activation JAK2/STAT3 PI3K/Akt/NFκB CTS-treated cells.CTS suppressing pathways altering Bcl-2/Bax family, which regulated these two pathways. may serve as potential therapeutic agent CCA.