Effects of the angiogenesis inhibitor angiostatin on the growth of CC531 colon carcinoma cells in vitro and in a laparoscopic animal model of peritoneal carcinomatosis.
BACKGROUND
As angiogenesis is one of the key steps in tumor growth, invasion, and metastasis, antiangiogenic therapy is supposed to be an attractive approach for antitumor treatment. We investigated the cytotoxic, anti-adhesive, and anti-invasive effects of angiostatin in vitro and on intraperitoneal tumor growth in a laparoscopic rat model of peritoneal carcinomatosis using CC531 colon adenocarcinoma cells.


METHODS
The in vitro adhesion and cytotoxicity assays were performed with microtiter plates, and the invasion assay with Transwell dual chambers. Normal saline was used as control. In in vivo experiments, CC531 adenocarcinoma cells were intraperitoneally given to Wistar Albino Glaxo rats after the establishment of a pneumoperitoneum. The animals received angiostatin in different doses intraperitoneally, and in some, angiostatin was additionally administered subcutaneously. Saline was used as control. After 21 days, the animals were euthanized to determine the intra-abdominal tumor weight.


RESULTS
In in vitro experiments, there was no effect of angiostatin on the viability of tumor cells in the cytotoxicity assay, but there was a significant inhibition of tumor cell adhesion and invasion (p<0.05 and p<0.01) in all angiostatin concentrations. In in vivo experiments, an intraperitoneal application of 20 microg angiostatin, but not 10 microg, significantly (p<0.005) decreased the intraperitoneal tumor weight compared with controls. This effect was most pronounced after the combined intraperitoneal and subcutaneous applications.


CONCLUSIONS
Angiostatin given intraperitoneally at a dose of 20 microg alone or in combination with subcutaneous application significantly diminishes intraperitoneal tumor growth in rats undergoing laparoscopy. This may offer additional therapeutic options for patients undergoing laparoscopic surgery for colorectal cancer.
Nestler
G
G
Department of Surgery, Faculty of Medicine, Otto-von-Guericke University Magdeburg, Leipziger Str. 44, 39120, Magdeburg, Germany. gnestler@hotmail.com
Schulz
H U
HU
Tautenhahn
J
J
Kuhn
R
R
Krüger
S
S
Lippert
H
H
Pross
M
M
D000230:Adenocarcinoma / Q000473:pathology; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D043168:Angiostatins / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D010535:Laparoscopy; D008297:Male; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010534:Peritoneal Neoplasms / Q000098:blood supply / Q000473:pathology*; D011028:Pneumoperitoneum, Artificial; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D020533:Angiogenesis Inhibitors; D043168:Angiostatins