Yongfei He1, Yanghong Li2, Tianyi Liang1, Shutian Mo1, Yuan Liao1, Zijun Chen1, Shuqi Zhao1, Qingfu Ran3, Chuangye Han1,4, Pham Thi Thai Hoa5. 1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China. 2. Department of Breast and Thyroid Surgery, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China. 3. Organizing Personnel Section, The First Affiliated Hospital of Guangxi Medical University, Nanning, China. 4. Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, China. 5. Zhuang & Yao Medicine Research and Development Center of Guangxi International Zhuang Medicine Hospital, Nanning, China.
Abstract
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. 2022 Journal of Gastrointestinal Oncology. All rights reserved.
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. 2022 Journal of Gastrointestinal Oncology. All rights reserved.
Authors: Jesus M Banales; Jose J G Marin; Angela Lamarca; Pedro M Rodrigues; Shahid A Khan; Lewis R Roberts; Vincenzo Cardinale; Guido Carpino; Jesper B Andersen; Chiara Braconi; Diego F Calvisi; Maria J Perugorria; Luca Fabris; Luke Boulter; Rocio I R Macias; Eugenio Gaudio; Domenico Alvaro; Sergio A Gradilone; Mario Strazzabosco; Marco Marzioni; Cédric Coulouarn; Laura Fouassier; Chiara Raggi; Pietro Invernizzi; Joachim C Mertens; Anja Moncsek; Sumera Rizvi; Julie Heimbach; Bas Groot Koerkamp; Jordi Bruix; Alejandro Forner; John Bridgewater; Juan W Valle; Gregory J Gores Journal: Nat Rev Gastroenterol Hepatol Date: 2020-06-30 Impact factor: 46.802
Authors: Choon Kiat Ong; Chutima Subimerb; Chawalit Pairojkul; Sopit Wongkham; Ioana Cutcutache; Willie Yu; John R McPherson; George E Allen; Cedric Chuan Young Ng; Bernice Huimin Wong; Swe Swe Myint; Vikneswari Rajasegaran; Hong Lee Heng; Anna Gan; Zhi Jiang Zang; Yingting Wu; Jeanie Wu; Ming Hui Lee; DaChuan Huang; Pauline Ong; Waraporn Chan-on; Yun Cao; Chao-Nan Qian; Kiat Hon Lim; Aikseng Ooi; Karl Dykema; Kyle Furge; Veerapol Kukongviriyapan; Banchob Sripa; Chaisiri Wongkham; Puangrat Yongvanit; P Andrew Futreal; Vajarabhongsa Bhudhisawasdi; Steve Rozen; Patrick Tan; Bin Tean Teh Journal: Nat Genet Date: 2012-05-06 Impact factor: 38.330