Effects of 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione on autophagy and the PI3K/AKT/mTOR signaling pathway in human cholangiocarcinoma QBC939 cells

Journal of Gastrointestinal Oncology

article

Yongfei He¹  Yanghong Li²  Tianyi Liang¹  Shutian Mo¹  Yuan Liao¹  Zijun Chen¹  Shuqi Zhao¹  Qingfu Ran³  Chuangye Han¹  Pham Thi Thai Hoa⁵ 

[1] Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University;Department of Breast and Thyroid Surgery, The Affiliated Hospital of Youjiang Medical University for Nationalities;Organizing Personnel Section, The First Affiliated Hospital of Guangxi Medical University;Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor;Zhuang & Yao Medicine Research and Development Center of Guangxi International Zhuang Medicine Hospital

关键词: 2-dodecyl-6-methoxycyclohexa-2;    5-diene-1;    4-dione (DMDD);    autophagy;    cholangiocarcinoma (CCA);    PI3K/AKT/mTOR;   

DOI  :  10.21037/jgo-22-298

学科分类：肿瘤学

来源: Pioneer Bioscience Publishing Company

【 摘 要 】

Background: 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) has been reported to have good antitumor effects. The aim of this study was to investigate whether DMDD induces apoptosis and autophagy in human cholangiocarcinoma (CCA) QBC939 cells and determine its effect on the PI3K/AKT/mTOR signaling pathway. Methods: QBC939 cells were cultured in vitro and changes in cell viability were detected by the Cell Counting Kit (CCK8) assay after treatment with different concentrations of DMDD for 24, 48, and 72 h. The cells were divided into control and DMDD-treated groups (treated concentrations were 10, 15, and 20 µM/L), and the cell cycle, apoptosis, and autophagic vesicles were assessed. The expression levels of PI3K, AKT, mTOR, microtubule-associated protein 1 light chain 3 beta (LC3-II)/I, Beclin-1, and P62 were detected by Western blot. A xenograft mouse model was constructed to detect the effect of DMDD on CCA. Results: The experimental results showed that DMDD was able to inhibit proliferation, migration, and invasion and induce cell cycle arrest and autophagy of QBC939 cells. In addition, DMDD decreased the protein expression of PI3K, AKT, and mTOR and increased the expression of LC3-II/I, Beclin-1, and P62. In mice, DMDD was able to inhibit the growth of tumors. Conclusions: DMDD inhibits CCA cell viability and induces cell cycle arrest and autophagy by a mechanism that may be related to the downregulation of the PI3K/AKT/mTOR signaling pathway.

【 授权许可】

Unknown