A proteinase inhibitor decreases tumor growth in a laparoscopic rat model.
BACKGROUND
The balance between proteolysis and protease inhibition in the formation and breakdown processes of the extracellular matrix plays a major role in tumor cell invasion. An understanding of this relationship gave rise to the therapeutic concept of lowering tumor cell invasion by inhibiting protease activity. Phosphoramidon is an unspecific proteinase inhibitor. This experimental study investigated the effect of intraperitoneal phosphoramidon administration on tumor growth in a laparoscopic rat model.


METHODS
In the first phase of the study, we investigated the influence of phosphoramidon on tumor cell invasion in a collagen matrix gel chamber in vitro. In a second experiment, a suspension of colon carcinoma cells (CC531) was introduced into the peritoneal cavity of male WAG rats. Prior to laparoscopy (at 6 mmHg for 20 min), the animals were randomized to two groups. At the start of laparoscopy, the test substance was applied intraperitoneally (group 1: controls, 1 ml 0.9% NaCl; group 2: 250 mg phosphoramidon in 1 ml 0.9% NaCl). Three weeks after the injection of tumor cells, the animals were autopsied and the tumor mass determined.


RESULTS
In comparison with the control group (tumor weight 7.42 +/- 1.01 g), intraperitoneal tumor growth in the experimental group was significantly (p < 0.001) reduced by the application of phosphoramidon (tumor weight, 3.22 +/- 1.06 g). Phosphoramidon also significantly (p < 0.05) reduced tumor cell invasion through the matrix gel.


CONCLUSIONS
The proteinase inhibitor phosphoramidon reduced tumor cell invasion in vitro and tumor cell growth in vivo in this laparoscopic rat model.
Pross
M
M
Department of Surgery, Otto von Guericke University, Leipziger Strasse 44, D-39120 Magdeburg, Germany. Matthias.Pross@medizin.uni-magdeburg.de
Lippert
H
H
Mantke
R
R
Krüger
S
S
Günther
T
T
Marusch
F
F
Halangk
W
W
Schulz
H U
HU
D000818:Animals; D003110:Colonic Neoplasms / Q000473:pathology* / Q000601:surgery; D006020:Glycopeptides / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D010535:Laparoscopy / Q000009:adverse effects; D008297:Male; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009366:Neoplasm Seeding; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured / Q000637:transplantation
D006020:Glycopeptides; D011480:Protease Inhibitors; C008890:phosphoramidon