title: Effects of rosiglitazone on the growth and lymphangiogenesis of human gastric cancer transplanted in nude mice.
abstract: Gastric cancer mainly metastasizes via lymphatic vessels. Thus, it is critical to identify efficacious chemopreventive agents for lymphangiogenesis. The present study was undertaken to explore the effects of rosiglitazone (ROSI) on the growth and lymphangiogenesis of human gastric cancer. We established a model of gastric cancer by subcutaneously inoculating the human gastric cancer cell line SGC-7901 into nude mice. Mice were randomly divided into 4 groups and each group received a different agent by oral gavage. The control group received normal saline and treatment groups received different doses of ROSI once every 2 days. The growth of the tumor in vivo was assessed by measuring tumor volume. After 42 days, the mice were sacrificed and the tumors were removed. H&E staining was used to observe the histomorphological features; immunohistochemistry staining for lymphatic vessel density (LVD) was used to evaluate tumor lymphangiogenesis, RT-PCR was performed to determine the mRNA expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor-3 (VEGFR-3), and western blotting was used to detect the protein expression of VEGF-C and VEGFR-3. Compared with the control group, all treatment groups had smaller tumor volume and higher tumor growth inhibitory rate every day. The number of typical tumor cells in the control group was higher compared to that in the treatment groups, and the highest level of LVD was found in the control group. Furthermore, both the expression of VEGF-C and VEGFR-3 mRNA and proteins in the control group were significantly higher compared to those in the treatment groups. Markedly, these changes were correlated in a dose-dependent manner with ROSI. These results demonstrated that, through simultaneously blocking the expression of VEGF-C and VEGFR-3, ROSI suppresses lymphangiogenesis. This may represent a powerful therapeutic approach for controlling gastric cancer cell growth and metastasis.
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Fang-Zhi
authors.initials: FZ
authors.lastname: Chen
authors.forename: Xi-Ming
authors.initials: XM
authors.lastname: Mo
authors.forename: Qing-Ping
authors.initials: QP
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042583:Lymphangiogenesis / Q000187:drug effects*; D008207:Lymphatic Metastasis / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000096:biosynthesis; D000077154:Rosiglitazone; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045162:Thiazolidinediones / Q000008:administration & dosage*; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000096:biosynthesis
chemical_list: D012333:RNA, Messenger; D045162:Thiazolidinediones; D042582:Vascular Endothelial Growth Factor C; C467483:vascular endothelial growth factor C, mouse; D000077154:Rosiglitazone; D040321:Vascular Endothelial Growth Factor Receptor-3