Endostar attenuates melanoma tumor growth via its interruption of b-FGF mediated angiogenesis

Lijia Xiao; ShuCai Yang; Jianhua Hao; Xue Yuan; Wei Luo; Liping Jiang; Yang Hu; Zhongping Fu; Yun Zhang; Chang Zou

doi:10.1016/j.canlet.2015.01.012

Endostar attenuates melanoma tumor growth via its interruption of b-FGF mediated angiogenesis

Cancer Lett. 2015 Apr 1;359(1):148-54. doi: 10.1016/j.canlet.2015.01.012. Epub 2015 Jan 15.

Authors

Lijia Xiao¹, ShuCai Yang², Jianhua Hao¹, Xue Yuan³, Wei Luo³, Liping Jiang³, Yang Hu³, Zhongping Fu³, Yun Zhang³, Chang Zou⁴

Affiliations

¹ Department of Clinical Laboratory, Nanshan affiliated Hospital of Guangdong Medical College, Shenzhen 518052, China.
² 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.
³ Department of Pharmacology, Jiangsu Simcere Pharmaceutical Research Institute, 699-18 Xuan Wu Avenue, Nanjing 210042, China.
⁴ 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.

PMID: 25597785
DOI: 10.1016/j.canlet.2015.01.012

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.

Keywords: Angiogenesis; Endostar; Melanoma; Targeted therapy; b-FGF.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiogenesis Inhibitors / biosynthesis
Angiogenesis Inhibitors / genetics
Angiogenesis Inhibitors / pharmacology*
Animals
Cell Line, Tumor
Cell Movement / drug effects
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Endostatins / biosynthesis
Endostatins / genetics
Endostatins / pharmacology*
Fibroblast Growth Factor 2 / metabolism*
Human Umbilical Vein Endothelial Cells / drug effects*
Human Umbilical Vein Endothelial Cells / metabolism
Humans
Melanoma, Experimental / blood supply*
Melanoma, Experimental / drug therapy*
Melanoma, Experimental / metabolism
Melanoma, Experimental / pathology
Mice
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Neovascularization, Pathologic*
Neovascularization, Physiologic / drug effects*
Phosphorylation
Recombinant Proteins
Signal Transduction / drug effects
Skin Neoplasms / blood supply*
Skin Neoplasms / drug therapy*
Skin Neoplasms / metabolism
Skin Neoplasms / pathology
Tumor Burden / drug effects
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

Angiogenesis Inhibitors
Endostatins
Recombinant Proteins
Fibroblast Growth Factor 2
MAPK1 protein, human
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
p38 Mitogen-Activated Protein Kinases
endostar protein