title: Endostar attenuates melanoma tumor growth via its interruption of b-FGF mediated angiogenesis.
abstract: To develop optimal therapeutics is one of the hotspots in both clinical and basic melanoma studies. Previous studies indicate that fibroblast growth factors (b-FGF/FGF-2), an angiogenesis inducer beyond VEGF, might be a potential drug target in melanoma. As a novel anti-angiogenesis peptide drug, Endostar has shown promising therapeutic efficacy in non-small cell lung cancer. However, the effect of Endostar on b-FGF-induced angiogenesis in melanoma is unraveled. To this end, both in vivo and in vitro experiments were conducted and it was found that treatment of Endostar could inhibit tumor growth, which was accompanied by decreased micro-vessel density and serum b-FGF levels in a mouse melanoma model. In addition, treatment with Endostar in blood vessel endothelial cells could reduce their proliferation, cell migration and tube formation capacity in a dosage-dependent manner. Moreover, treatment of Endostar could also attenuate b-FGF-activated phosphorylation of p38 and ERK1/2 in HUVECs. These findings indicate that Endostar might exert its anti-tumor effect via suppressing b-FGF-induced angiogenesis and b-FGF-activated MAPK signaling pathway, suggesting that Endostar might be a potential choice for clinical melanoma treatment.
authors.affiliation: Department of Clinical Laboratory, Nanshan affiliated Hospital of Guangdong Medical College, Shenzhen 518052, China.
authors.forename: Lijia
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Department of Surgery, School of Medicine, The Chinese University of Hong Kong, Hong Kong, China; Department of Laboratory Medicine, Yijishan Hospital, Wannan Medical College, Wuhu 241001, Anhui, China.
authors.forename: ShuCai
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, Nanshan affiliated Hospital of Guangdong Medical College, Shenzhen 518052, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Hao
authors.affiliation: Department of Pharmacology, Jiangsu Simcere Pharmaceutical Research Institute, 699-18 Xuan Wu Avenue, Nanjing 210042, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Pharmacology, Jiangsu Simcere Pharmaceutical Research Institute, 699-18 Xuan Wu Avenue, Nanjing 210042, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, Jiangsu Simcere Pharmaceutical Research Institute, 699-18 Xuan Wu Avenue, Nanjing 210042, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, Jiangsu Simcere Pharmaceutical Research Institute, 699-18 Xuan Wu Avenue, Nanjing 210042, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Jiangsu Simcere Pharmaceutical Research Institute, 699-18 Xuan Wu Avenue, Nanjing 210042, China.
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Pharmacology, Jiangsu Simcere Pharmaceutical Research Institute, 699-18 Xuan Wu Avenue, Nanjing 210042, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen 518020, China; Department of Pharmacology, Jiangsu Simcere Pharmaceutical Research Institute, 699-18 Xuan Wu Avenue, Nanjing 210042, China. Electronic address: zouchang.cuhk@gmail.com.
authors.forename: Chang
authors.initials: C
authors.lastname: Zou
mesh_terms: D020533:Angiogenesis Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D043169:Endostatins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010766:Phosphorylation; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D043169:Endostatins; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; C522911:endostar protein
keywords: Angiogenesis; Endostar; Melanoma; Targeted therapy; b-FGF