title: NSK-01105, a novel sorafenib derivative, inhibits human prostate tumor growth via suppression of VEGFR2/EGFR-mediated angiogenesis.
abstract: The purpose of this study is to investigate the anti-angiogenic activities of NSK-01105, a novel sorafenib derivative, in in vitro, ex vivo and in vivo models, and explore the potential mechanisms. NSK-01105 significantly inhibited vascular endothelial growth factor (VEGF)-induced migration and tube formation of human umbilical vein endothelial cells at non-cytotoxic concentrations as shown by wound-healing, transwell migration and endothelial cell tube formation assays, respectively. Cell viability and invasion of LNCaP and PC-3 cells were significantly inhibited by cytotoxicity assay and matrigel invasion assay. Furthermore, NSK-01105 also inhibited ex vivo angiogenesis in matrigel plug assay. Western blot analysis showed that NSK-01105 down-regulated VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR2) and the activation of epidermal growth factor receptor (EGFR). Tumor volumes were significantly reduced by NSK-01105 at 60 mg/kg/day in both xenograft models. Immunohistochemical staining demonstrated a close association between inhibition of tumor growth and neovascularization. Collectively, our results suggest a role of NSK-01105 in treatment for human prostate tumors, and one of the potential mechanisms may be attributed to anti-angiogenic activities.
authors.affiliation: School of Life Science and Bio-pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Long-acting and Targeting Drug Delivery System, Non-clinical Research Department, Luye Pharma Group Ltd., Yantai, Shandong 264003, China; School of Pharmaceutical Sciences and Institute of Material Medical, Binzhou Medical University, Yantai, Shandong 264005, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Long-acting and Targeting Drug Delivery System, Non-clinical Research Department, Luye Pharma Group Ltd., Yantai, Shandong 264003, China; School of Pharmacy, Yantai University, Yantai, Shandong 264005, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Long-acting and Targeting Drug Delivery System, Non-clinical Research Department, Luye Pharma Group Ltd., Yantai, Shandong 264003, China; School of Pharmacy, Yantai University, Yantai, Shandong 264005, China.
authors.forename: Guangying
authors.initials: G
authors.lastname: Du
authors.affiliation: State Key Laboratory of Long-acting and Targeting Drug Delivery System, Non-clinical Research Department, Luye Pharma Group Ltd., Yantai, Shandong 264003, China.
authors.forename: Jianzhao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Affiliated Hospital of Medical College of Qingdao University, Qingdao, Shandong 266001, China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: School of Life Science and Bio-pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China.
authors.forename: Jinghai
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Long-acting and Targeting Drug Delivery System, Non-clinical Research Department, Luye Pharma Group Ltd., Yantai, Shandong 264003, China; School of Pharmacy, Yantai University, Yantai, Shandong 264005, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Tian
mesh_terms: D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055808:Drug Discovery; D004789:Enzyme Activation / Q000187:drug effects*; D066246:ErbB Receptors / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000473:pathology; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D000077157:Sorafenib; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; C000601029:NSK-01105; D010671:Phenylurea Compounds; D011799:Quinazolines; D009536:Niacinamide; D000077157:Sorafenib; D066246:ErbB Receptors; D040301:Vascular Endothelial Growth Factor Receptor-2