title: In vitro and in vivo study of hydralazine, a potential anti-angiogenic agent.
abstract: Hydralazine (HYD), an old routine clinical anti-hypertension drug, is rarely used in clinic nowadays. Since the strategy of repositioning old drugs was put forward, HYD has been reported to possess various biological activities, including antitumor efficacy and reducing intra-tumor microvessel. Here, we investigated that whether HYD had the ability of anti-angiogeneis and its underlying mechanism. Cells proliferation, wound-healing, Transwell migration and invasion, tube formation and rat aortic ring assays in vitro and chicken chorioallantoic membrane (CAM) model in vivo were designed to investigated HYD's anti-angiogenic effect. Levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were assessed by enzyme-linked immune sorbent assay (ELISA). Hepatocellular carcinoma (HCC) mice model was used to evaluate HYD's effect on tumor growth and microvessel density. Our results showed that HYD not only inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, wound-healing, Transwell migration and invasion and tube formation, but also suppressed the microvessel outgrowth of rat aortic ring in vitro and the neovascularzation of CAM in vivo. Furthermore, we demonstrated that HYD attenuated tumor angiogenesis and tumor growth. In the co-culture system of Transwell migration, the secretion of VEGF and bFGF was reduced by HYD respectively. In sum, our data indicate that HYD has the pharmacological effect of ant-angiogenesis by interference with VEGF and bFGF signaling pathways in endothelial cells. These findings suggest that HYD might be a promising angiogenesis inhibitor and a potential effective therapeutic agent for cancer therapy.
authors.affiliation: The Key Lab of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Quanwei
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: The Key Lab of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Zhexuan
authors.initials: Z
authors.lastname: Lin
authors.affiliation: The Key Lab of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Xiukai
authors.initials: X
authors.lastname: Yin
authors.affiliation: The Key Lab of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Tang
authors.affiliation: The Key Lab of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Luo
authors.affiliation: The Key Lab of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: The Key Lab of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Key Lab of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address: whluo@stu.edu.cn.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Luo
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D006830:Hydralazine
keywords: Anti-angiogenesis; Hepatocellular carcinoma; Hydralazine; VEGF; bFGF