Min Xiao1,2,3, Chunhua Lin4, Zhaoxin Yang1,2,3, Shuhong Tian1,2,3, Yanan Huang1, Jian Fu1. 1. Hainan Medical College Preclinical Pharmacology Laboratory Hainan, P. R. China. 2. Center for Drug Safety Evaluation Research of Hainan Province Hainan, P. R. China. 3. Hainan Provincial Key Laboratory of Preclinical Pharmacology and Toxicology HaiKou 571199, Hainan, P. R. China. 4. Guo Rui Yinuo Drug Safety Evaluation and Research Co., Ltd Xixian New Area, Xian Yang 712000, Shaanxi, P. R. China.
Abstract
OBJECTIVE: 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. METHODS: 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 in vivo was evaluated by assessing tumor volume and bioluminescence value. RESULTS: 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. CONCLUSION: 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 in vivo and in vitro. AJTR
OBJECTIVE: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. METHODS: 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 in vivo was evaluated by assessing tumor volume and bioluminescence value. RESULTS: 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. CONCLUSION: 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 in vivo and in vitro. AJTR
Authors: Abdel-Ghany A El-Helby; Helmy Sakr; Ibrahim H Eissa; Hamada Abulkhair; Ahmed A Al-Karmalawy; Khaled El-Adl Journal: Arch Pharm (Weinheim) Date: 2019-08-25 Impact factor: 3.751
Authors: Pan Zhang; Ze-Lin Lai; Hui-Fen Chen; Min Zhang; An Wang; Tao Jia; Wen-Qin Sun; Xi-Min Zhu; Xiao-Feng Chen; Zheng Zhao; Jun Zhang Journal: J Exp Clin Cancer Res Date: 2017-12-22