He Yongfei, Li Yanghong, Liang Tianyi, Mo Shutian, Liao Yuan, Chen Zijun, Zhao Shuqi, Ran Qingfu, Han Chuangye, Hoa Pham Thi Thai
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Breast and Thyroid Surgery, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
J Gastrointest Oncol. 2022 Jun;13(3):1423-1432. doi: 10.21037/jgo-22-298.
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.
QBC939 cells were cultured 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.
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.
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.
据报道，2-十二烷基-6-甲氧基环己-2,5-二烯-1,4-二酮（DMDD）具有良好的抗肿瘤作用。本研究旨在探讨DMDD是否能诱导人胆管癌（CCA）QBC939细胞凋亡和自噬，并确定其对PI3K/AKT/mTOR信号通路的影响。
培养QBC939细胞，用不同浓度的DMDD处理24、48和72小时后，通过细胞计数试剂盒（CCK8）检测细胞活力变化。将细胞分为对照组和DMDD处理组（处理浓度为10、15和20 μM/L），评估细胞周期、凋亡和自噬小泡。通过蛋白质印迹法检测PI3K、AKT、mTOR、微管相关蛋白1轻链3β（LC3-II）/I、Beclin-1和P62的表达水平。构建异种移植小鼠模型以检测DMDD对CCA的影响。
实验结果表明，DMDD能够抑制QBC939细胞的增殖、迁移和侵袭，并诱导细胞周期停滞和自噬。此外，DMDD降低了PI3K、AKT和mTOR的蛋白表达，增加了LC3-II/I、Beclin-1和P62的表达。在小鼠中，DMDD能够抑制肿瘤生长。
DMDD通过一种可能与PI3K/AKT/mTOR信号通路下调有关的机制抑制CCA细胞活力并诱导细胞周期停滞和自噬。
