Attenuation by cyclic phosphatidic acid of peritoneal metastasis of azoxymethane-induced intestinal cancers in Wistar rats.
The effect of cyclic phosphatidic acid, a unique analogue of lysophosphatidic acid, on the induction of bombesin-enhanced peritoneal metastases from intestinal adenocarcinomas induced by azoxymethane was investigated in male Wistar rats. Rats were given 10 weekly injections of azoxymethane (7.4 mg/kg body weight, s.c.) and of bombesin (40 microg/kg body weight, s.c.) every other day from the start of the experiment, and from week 16, they received injections of cyclic phosphatidic acid (3 or 6 mg/kg body weight, s.c.) every other day until the end of the experiment in week 45. Cyclic phosphatidic acid at both dosages significantly decreased the incidence of bombesin-enhanced cancer metastases to the peritoneum but had little or no effect on the location, histologic type, depth of involvement or infiltrating growth patterns of the tumors. Cyclic phosphatidic acid at either dose decreased significantly the incidence of lymphatic vessel invasion of adenocarcinomas and the activity of RhoA protein in the tumors, both of which were enhanced by bombesin. Our findings indicate that cyclic phosphatidic acid inhibits cancer metastasis through inhibition of RhoA protein activation.
Ishihara
Ryu
R
Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan. ishihara-ry@mc.pref.osaka.jp
Tatsuta
Masaharu
M
Iishi
Hiroyasu
H
Baba
Miyako
M
Uedo
Noriya
N
Higashino
Koji
K
Mukai
Mutsuko
M
Ishiguro
Shingo
S
Kobayashi
Susumu
S
Murakami-Murofushi
Kimiko
K
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D001397:Azoxymethane; D000242:Cyclic AMP / Q000096:biosynthesis; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008246:Lysophospholipids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009361:Neoplasm Invasiveness; D010534:Peritoneal Neoplasms / Q000517:prevention & control / Q000556:secondary*; D051381:Rats; D017208:Rats, Wistar; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors*
D008246:Lysophospholipids; D000242:Cyclic AMP; D020742:rhoA GTP-Binding Protein; D001397:Azoxymethane