Background: Precursor of nerve growth factor (proNGF) was previously considered biologically inactive; however, it has recently been identified as having important roles in the pathology of cancer development. Aim: This study aimed to explore the therapeutic effects of proNGF siRNA on the proliferation, invasion, and anoikis of pancreatic cancer cells and determine the functions of proNGF. Methods: Pancreatic ductal adenocarcinoma (PDAC) and paired paracancerous tissue samples were collected from 60 patients for evaluation of proNGF expression by immunohistochemistry staining, qPCR, and western blotting. PDAC cell proliferation, migration, apoptosis, and anoikis following proNGF siRNA knockdown were investigated in two pancreatic cancer cell lines, Panc-1 and Bxpc-3, using BrdU incorporation assays, EdU staining, Ki-67 immunofluorescence (IF) staining, wound-healing assays, transwell invasion assays, and EthD-1 IF staining. Autophagy-related proteins were also measured by western blotting. Results: Levels of proNGF protein were higher in pancreatic cancer tissues and cells lines than those in paracancerous tissues and normal pancreatic duct epithelial cells, respectively. In vitro, ProNGF knockdown by siRNA led to significantly reduced cell proliferation, remarkably inhibited wound-healing, and reduced the number of invaded PDAC cells in migration and transwell assays. Treatment with proNGF siRNA also downregulated ATG5 and Beclin 1 protein levels, increased those of P62, and increased EthD-1 staining in PDAC cells. Conclusion: ProNGF expression is elevated in PDAC tissues and cell lines, and proNGF siRNA can inhibit cell proliferation, migration, and invasion, and promote anoikis of pancreatic cancer cells, in which decreased proNGF may participate.
基金：
Scientific Research Foundation of Yunnan Education Department [2016ZDX011]; Yunnan Scientific and Technology Committee and Kunming Medical University, P.R. China [2017FE468(-107)]; Yunnan Health Training Special Project of High Level Talents [D-2017032]
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类|3 区医学
小类|3 区医学：研究与实验3 区药学
最新[2023]版：
大类|2 区医学
小类|1 区药学2 区医学：研究与实验
JCR分区：
出版当年[2018]版：
Q1PHARMACOLOGY & PHARMACYQ2MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q1MEDICINE, RESEARCH & EXPERIMENTALQ1PHARMACOLOGY & PHARMACY
第一作者机构：[1]First Peoples Hosp Yunnan Prov, Dept Gen Surg 2, Kunming 650032, Yunnan, Peoples R China[2]Kunming Univ Sci & Technol, Affiliated Hosp, Kunming 650032, Yunnan, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]First Peoples Hosp Yunnan Prov, Dept Gen Surg 2, Kunming 650032, Yunnan, Peoples R China[2]Kunming Univ Sci & Technol, Affiliated Hosp, Kunming 650032, Yunnan, Peoples R China[3]First Peoples Hosp Yunnan Prov, Dept Ophthalmol, Kunming 650032, Yunnan, Peoples R China[*1]Department of Ophthalmology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, 157 Jinbi Road, Kunming 650032, China.[*2]Second Department of General Surgery, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, 157 Jinbi Road, Kunming 650032, China.
推荐引用方式(GB/T 7714)：
Xu Jianbiao,Song Jianlin,Yang Xiaochun,et al.ProNGF siRNA inhibits cell proliferation and invasion of pancreatic cancer cells and promotes anoikis[J].BIOMEDICINE & PHARMACOTHERAPY.2019,111:1066-1073.doi:10.1016/j.biopha.2019.01.002.
APA：
Xu, Jianbiao,Song, Jianlin,Yang, Xiaochun,Guo, Jianhui,Wang, Tongmin&Zhuo, Weidong.(2019).ProNGF siRNA inhibits cell proliferation and invasion of pancreatic cancer cells and promotes anoikis.BIOMEDICINE & PHARMACOTHERAPY,111,
MLA：
Xu, Jianbiao,et al."ProNGF siRNA inhibits cell proliferation and invasion of pancreatic cancer cells and promotes anoikis".BIOMEDICINE & PHARMACOTHERAPY 111.(2019):1066-1073
医学