Angiogenesis inhibitor TNP-470 suppresses growth of peritoneal disseminating foci of human colon cancer line Lovo. 2002

Ying-Fang Fan, and Zong-Hai Huang
Department of Surgery, Zhujiang Hospital, The First Military Medical University, Guangzhou 510282, Guangdong Province, China. fyfnj@yahoo.com.cn

OBJECTIVE To study the effect of angiogenesis inhibitor TNP-470 on peritoneal dissemination of colon cancer in nude mice. METHODS The MTT assay was used to evaluate the inhibitory effect of TNP-470 on human colon cancer cell line Lovo. Lovo cells were injected into the peritoneal cavity of BABL/C nu/nu mice and the models of peritoneal dissemination were developed. Thirty nude mice were randomly divided into control and TNP-470-treated group. In TNP-470-treated group, TNP-470 was injected subcutaneously every other day from day 1 until sacrifice or death (30 mg x kg(-1)). The control group received a sham injection of the same volume saline solution. RESULTS In vitro, TNP-470 inhibited the growth of Lovo cells, with its IC50 at 2.14 X 10(2) microg x L(-1). In vitro, TNP-470 demonstrated growth inhibition of tumors. Mice body weight and abdominal circumferences were significantly different between TNP-470-treated group (24.5+/-3.2 g, 7.0+/-1.1 cm) and control group (29.5+/-2.1 g, 10.3+/-1.5 cm), P=0.005 and P=0.001. The number of disseminated foci was significantly different between the control group (92.1+/-20.6) and the TNP-470-treated group (40.3+/-12.3), P<0.001. The maximal size of foci was significantly smaller in TNP-470-treated group (3.3+/-0.7 mm) than that of control (7.3+/-2.3 mm), P=0.004. Mean survival time was significantly longer in TNP-470-treated group(98.00+/-12.06 d) than that in control group (41.86+/-9.51 d), P<0.001. CONCLUSIONS Angiogenesis inhibitor TNP-470 might be effective in treating peritoneal dissemination of colon cancer and improve the survival rate of nude mice.

UI MeSH Term Description Entries
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008819 Mice, Nude Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses. Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D010537 Peritoneum A membrane of squamous EPITHELIAL CELLS, the mesothelial cells, covered by apical MICROVILLI that allow rapid absorption of fluid and particles in the PERITONEAL CAVITY. The peritoneum is divided into parietal and visceral components. The parietal peritoneum covers the inside of the ABDOMINAL WALL. The visceral peritoneum covers the intraperitoneal organs. The double-layered peritoneum forms the MESENTERY that suspends these organs from the abdominal wall. Parietal Peritoneum,Peritoneum, Parietal,Peritoneum, Visceral,Visceral Peritoneum,Parametrium,Parametriums
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D003110 Colonic Neoplasms Tumors or cancer of the COLON. Cancer of Colon,Colon Adenocarcinoma,Colon Cancer,Cancer of the Colon,Colon Neoplasms,Colonic Cancer,Neoplasms, Colonic,Adenocarcinoma, Colon,Adenocarcinomas, Colon,Cancer, Colon,Cancer, Colonic,Cancers, Colon,Cancers, Colonic,Colon Adenocarcinomas,Colon Cancers,Colon Neoplasm,Colonic Cancers,Colonic Neoplasm,Neoplasm, Colon,Neoplasm, Colonic,Neoplasms, Colon
D003510 Cyclohexanes Six-carbon alicyclic hydrocarbons.
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077609 O-(Chloroacetylcarbamoyl)fumagillol Semisynthetic analog of fumagillin (a cyclohexane-sesquiterpene antibiotic isolated from ASPERGILLUS FUMIGATUS) that inhibits angiogenesis. 5-Methoxy-4-(2-methyl-3-(3-methyl-2-butenyl)oxiranyl)-1-oxaspiro(2,5)oct-6-yl(chloroacetyl) carbamate,AGM 1470,AGM-1470,Caplostatin,TNP 470,TNP-470,AGM1470,TNP470
D000230 Adenocarcinoma A malignant epithelial tumor with a glandular organization. Adenocarcinoma, Basal Cell,Adenocarcinoma, Granular Cell,Adenocarcinoma, Oxyphilic,Adenocarcinoma, Tubular,Adenoma, Malignant,Carcinoma, Cribriform,Carcinoma, Granular Cell,Carcinoma, Tubular,Adenocarcinomas,Adenocarcinomas, Basal Cell,Adenocarcinomas, Granular Cell,Adenocarcinomas, Oxyphilic,Adenocarcinomas, Tubular,Adenomas, Malignant,Basal Cell Adenocarcinoma,Basal Cell Adenocarcinomas,Carcinomas, Cribriform,Carcinomas, Granular Cell,Carcinomas, Tubular,Cribriform Carcinoma,Cribriform Carcinomas,Granular Cell Adenocarcinoma,Granular Cell Adenocarcinomas,Granular Cell Carcinoma,Granular Cell Carcinomas,Malignant Adenoma,Malignant Adenomas,Oxyphilic Adenocarcinoma,Oxyphilic Adenocarcinomas,Tubular Adenocarcinoma,Tubular Adenocarcinomas,Tubular Carcinoma,Tubular Carcinomas

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