title: Effect of BZG-4000, a novel multi-targeted kinase inhibitor with potent anticancer activity, on a hepatocellular carcinoma xenograft model.
abstract: The present study was to synthesize a novel multi-targeted kinase inhibitor and evaluated its anticancer effects on a hepatocellular carcinoma xenograft model. In our study, in vivo efficacy was determined in nude mice bearing HuH7 human HCC xenografts. The mice were randomly divided into the following five groups with the use of a randomization chart (n = 8 in each group): high-dose BZG-4000 group, medium-dose BZG-4000 group, low-dose BZG-4000 group, sorafenib group, and model group. Tumor size measurements included the length (L) and width (W) measured with calipers, and tumor volume was calculated as (LW∧2)/2. Tumor tissues slides were hematoxylin and eosin (HE) stained for histopathological examination. Immunohistochemistry detected CD31 expression, and Western blotting measured VEGF protein expression. We found that when BZG-4000 was administered orally to xenograft HuH7 nude mice, tumor growth was inhibited and significant tumor shrinkage was evident. After oral administration of BZG-4000 at 40 mg/kg/day, the tumor weight and volume were significantly lower than tumors of the sorafenib group. BZG-4000 considerably decreased the expression of CD31 and VEGF in tumors compared to tumors treated with positive control drug. It was concluded that BZG-4000 has the potential to inhibit the tumorigenesis of hepatocellular carcinoma in vivo by decreasing the expression of CD31 and VEGF.
authors.affiliation: The First Affiliated Hospital, School of Medicine, Zhejiang University, 310003. Hangzhou, China.
authors.forename: Yun-Qing
authors.initials: YQ
authors.lastname: Qiu
authors.affiliation: College of Food Science and Biotechnology, Zhejiang Gongshang University, 310012. Hangzhou, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Fujian Haixi Pharmaceuticals Co., Ltd. 350002, Fuzhou, China.
authors.forename: Xin-Shan
authors.initials: XS
authors.lastname: Kang
authors.affiliation: Zhejiang Beta Pharma Co., Ltd. 311100. Hangzhou, China.
authors.forename: Lie-Ming
authors.initials: LM
authors.lastname: Ding
authors.affiliation: The First Affiliated Hospital, School of Medicine, Zhejiang University, 310003. Hangzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.affiliation: Zhejiang Beta Pharma Co., Ltd. 311100. Hangzhou, China.
authors.forename: Fen-Lai
authors.initials: FL
authors.lastname: Tan
authors.affiliation: The First Affiliated Hospital, School of Medicine, Zhejiang University, 310003. Hangzhou, China.
authors.forename: Dan-Feng
authors.initials: DF
authors.lastname: Deng
mesh_terms: D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004334:Drug Administration Schedule; D015870:Gene Expression; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D000077157:Sorafenib; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; C000602134:BZG-4000; D010671:Phenylurea Compounds; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D009536:Niacinamide; D000077157:Sorafenib