Xiao Min, Lin Chunhua, Yang Zhaoxin, Tian Shuhong, Huang Yanan, Fu Jian
Hainan Medical College Preclinical Pharmacology Laboratory Hainan, P. R. China.
Center for Drug Safety Evaluation Research of Hainan Province Hainan, P. R. China.
Am J Transl Res. 2021 Jan 15;13(1):73-87. eCollection 2021.
Gastric cancer is a potential malignant tumor. Extensive research has shown that apoptosis and autophagy are important mechanisms of cancer pathogenesis. This study aimed to explore the role and mechanism of TDB in apoptosis and autophagy in MGC-803 cells.
In cell experiments, the proliferation, apoptosis and autophagy of MGC-803 cells were evaluated by the MTT assay, TUNEL, flow cytometry, MDC, and TEM. Through molecular experiments, the TDB-induced apoptosis and autophagy effects were evaluated by examining the levels of Cleaved-PARP/PARP, Cleaved-caspase3/procaspase3, Beclin-1, p62 and the ratio of LC3-II/LC3-I. At the animal level, the anti-tumor effect of TDB was evaluated by assessing tumor volume and bioluminescence value.
Regarding mechanism, TDB induces apoptosis and autophagy through PI3K/AKT/mTOR. At the same time, more importantly, TDB promotes 3-methyladenine or autophagy activator rapamycin-mediated. The induced proliferation inhibition and pro-apoptosis effect, which inhibit autophagy and induce an increase in apoptosis.
TDB may up-regulate PARP, Cleaved Caspase-3, Beclin1 and LC3B and down-regulate the expression of P62 and other apoptosis and autophagy genes through the activation of PI3K/AKT/mTOR pathway signalling proteins, leading to autophagy-dependent apoptosis. At the animal level, TDB has good anti-tumor efficacy in vivo. In summary, TDB has potential anti-tumor efficacy and .
胃癌是一种潜在的恶性肿瘤。广泛研究表明，凋亡和自噬是癌症发病机制的重要机制。本研究旨在探讨TDB在MGC-803细胞凋亡和自噬中的作用及机制。
在细胞实验中，通过MTT法、TUNEL法、流式细胞术、MDC法和透射电镜评估MGC-803细胞的增殖、凋亡和自噬。通过分子实验，通过检测Cleaved-PARP/PARP、Cleaved-caspase3/procaspase3、Beclin-1、p62水平及LC3-II/LC3-I比值评估TDB诱导的凋亡和自噬作用。在动物水平，通过评估肿瘤体积和生物发光值评估TDB的抗肿瘤作用。
在机制方面，TDB通过PI3K/AKT/mTOR诱导凋亡和自噬。同时，更重要的是，TDB促进3-甲基腺嘌呤或自噬激活剂雷帕霉素介导的作用。诱导的增殖抑制和促凋亡作用，抑制自噬并诱导凋亡增加。
TDB可能通过激活PI3K/AKT/mTOR信号通路蛋白上调PARP、Cleaved Caspase-3、Beclin1和LC3B，下调P62等凋亡和自噬基因的表达，导致自噬依赖性凋亡。在动物水平，TDB在体内具有良好的抗肿瘤疗效。总之，TDB具有潜在的抗肿瘤疗效。
