KMT2D deficiency enhances the anti-cancer activity of L48H37 in pancreatic ductal adenocarcinoma
KMT2D deficiency enhances the anti-cancer activity of L48H37 in pancreatic ductal adenocarcinoma作者机构：Department of GastroenterologyShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 201620China Shanghai Key Laboratory of Pancreatic DiseasesShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 201620China
出 版 物：《World Journal of Gastrointestinal Oncology》 (世界胃肠肿瘤学杂志（英文版）（电子版）)
年 卷 期：2019年第11卷第8期
页 面：599-621页
核心收录：
学科分类：10[医学]
主 题：Pancreatic neoplasms Curcumin analog Histone methyltransferase 2D Therapeutic effects Bioinformatics
摘 要：BACKGROUND Novel therapeutic strategies are urgently needed for patients with a delayed diagnosis of pancreatic ductal adenocarcinoma(PDAC)in order to improve their chances of *** studies have shown potent anti-neoplastic effects of curcumin and its *** addition,the role of histone methyltransferases on cancer therapeutics has also been ***,the relationship between these two factors in the treatment of pancreatic cancer remains *** working hypothesis was that L48H37,a novel curcumin analog,has better efficacy in pancreatic cancer cell growth inhibition in the absence of histonelysine N-methyltransferase 2D(KMT2D).AIM To determine the anti-cancer effects of L48H37 in PDAC,and the role of KMT2D on its therapeutic *** The viability and proliferation of primary(PANC-1 and MIA PaCa-2)and metastatic(SW1990 and ASPC-1)PDAC cell lines treated with L48H37 was determined by CCK8 and colony formation ***,mitochondrial membrane potential(MMP),reactive oxygen species(ROS)levels,and cell cycle profile were determined by staining the cells with Annexin-V/7-AAD,JC-1,DCFH-DA,and PI respectively,as well as flow cytometric *** vitro migration was assessed by the wound healing *** protein and mRNA levels of relevant factors were analyzed using Western blotting,immunofluorescence and real time-quantitative *** in situ expression of KMT2D in both human PDAC and paired adjacent normal tissues was determined by *** vivo tumor xenografts were established by injecting nude mice with PDAC *** analyses were also conducted using gene expression databases and *** L48H37 inhibited the proliferation and induced apoptosis in SW1990 and ASPC-1 cells in a dose-and time-dependent manner,while also reducing MMP,increasing ROS levels,arresting cell cycle at the G2/M stages and activating the endoplasmic reticulum(ER)stress-associated protein kinase RNA-like endoplasmic
维普期刊数据库