Angiogenesis inhibitor TNP-470 suppresses growth of peritoneal disseminating foci of human colon cancer line Lovo.
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.
Fan
Ying-Fang
YF
Department of Surgery, Zhujiang Hospital, The First Military Medical University, Guangzhou 510282, Guangdong Province, China. fyfnj@yahoo.com.cn
Huang
Zong-Hai
ZH
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003510:Cyclohexanes; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D010537:Peritoneum / Q000473:pathology; D012717:Sesquiterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D020533:Angiogenesis Inhibitors; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol