CC-223, NSC781406, and BGT226 Exerts a Cytotoxic Effect Against Pancreatic Cancer Cells via mTOR Signaling
作者： Yangyang Guo , Hengyue Zhu , Min Weng , Hewei Zhang , Cheng Wang
DOI: 10.3389/FPHAR.2020.580407
关键词: Glycolysis 、 In vivo 、 Carbohydrate metabolism 、 Cancer research 、 Gene knockdown 、 PI3K/AKT/mTOR pathway 、 Pancreatic cancer 、 Mechanism (biology) 、 Cytotoxic T cell 、 Medicine
摘要: The mTOR signaling pathway is abnormally activated in pancreatic cancer and related to tumor glucose metabolism. However, its specific regulation mechanism still unclear. Therefore, this study aims investigate whether Sestrin2 affects the metabolism of by modulating signal then biological behavior. We have observed that l-leucine can promote proliferation cells increase expression p-mTOR proteins. In order further role cancer, we conducted overexpression pharmacological inhibition experiments. found glycolysis their proliferation. This effect be eliminated inhibitors. Finally, knockdown could inhibit growth vivo. conclusion, these findings suggest may occurrence development through signaling.
frontiersin.org
sci-hub.st 参考文章(27)
Andrei V. Budanov, Michael Karin, p53 Target Genes Sestrin1 and Sestrin2 Connect Genotoxic Stress and mTOR Signaling Cell. ,vol. 134, pp. 451- 460 ,(2008) , 10.1016/J.CELL.2008.06.028
Min Peng, Na Yin, Ming O. Li, Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling. Cell. ,vol. 159, pp. 122- 133 ,(2014) , 10.1016/J.CELL.2014.08.038
Suchithra Menon, Christian C. Dibble, George Talbott, Gerta Hoxhaj, Alexander J. Valvezan, Hidenori Takahashi, Lewis C. Cantley, Brendan D. Manning, Spatial Control of the TSC Complex Integrates Insulin and Nutrient Regulation of mTORC1 at the Lysosome Cell. ,vol. 156, pp. 771- 785 ,(2014) , 10.1016/J.CELL.2013.11.049
Andrei V. Budanov, Stress-Responsive Sestrins Link p53 with Redox Regulation and Mammalian Target of Rapamycin Signaling Antioxidants & Redox Signaling. ,vol. 15, pp. 1679- 1690 ,(2011) , 10.1089/ARS.2010.3530
Bo Kong, Christoph W Michalski, Jörg Kleeff, Tumor initiating cells in pancreatic cancer: A critical view. World Journal of Stem Cells. ,vol. 1, pp. 8- 10 ,(2009) , 10.4252/WJSC.V1.I1.8
Lynne Chantranupong, Rachel L. Wolfson, Jose M. Orozco, Robert A. Saxton, Sonia M. Scaria, Liron Bar-Peled, Eric Spooner, Marta Isasa, Steven P. Gygi, David M. Sabatini, The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. Cell Reports. ,vol. 9, pp. 1- 8 ,(2014) , 10.1016/J.CELREP.2014.09.014
Hui Chang, Xiaoli Peng, Qian Bai, Yong Zhou, Xiaoping Yu, Qianyong Zhang, Jundong Zhu, Mantian Mi, Ampelopsin suppresses breast carcinogenesis by inhibiting the mTOR signalling pathway Carcinogenesis. ,vol. 35, pp. 1847- 1854 ,(2014) , 10.1093/CARCIN/BGU118
Boxiao Ding, Anita Parmigiani, Chen Yang, Andrei V Budanov, Sestrin2 facilitates death receptor-induced apoptosis in lung adenocarcinoma cells through regulation of XIAP degradation. Cell Cycle. ,vol. 14, pp. 3231- 3241 ,(2015) , 10.1080/15384101.2015.1084447
Joseph M. Herman, Michael J. Swartz, Charles C. Hsu, Jordan Winter, Timothy M. Pawlik, Elizabeth Sugar, Ray Robinson, Daniel A. Laheru, Elizabeth Jaffee, Ralph H. Hruban, Kurtis A. Campbell, Christopher L. Wolfgang, Fariba Asrari, Ross Donehower, Manuel Hidalgo, Luis A. Diaz, Charles Yeo, John L. Cameron, Richard D. Schulick, Ross Abrams, Analysis of Fluorouracil-Based Adjuvant Chemotherapy and Radiation After Pancreaticoduodenectomy for Ductal Adenocarcinoma of the Pancreas: Results of a Large, Prospectively Collected Database at the Johns Hopkins Hospital Journal of Clinical Oncology. ,vol. 26, pp. 3503- 3510 ,(2008) , 10.1200/JCO.2007.15.8469
Jichun Yang, Yujing Chi, Brant R Burkhardt, Youfei Guan, Bryan A Wolf, Leucine metabolism in regulation of insulin secretion from pancreatic beta cells Nutrition Reviews. ,vol. 68, pp. 270- 279 ,(2010) , 10.1111/J.1753-4887.2010.00282.X