Abstract:
: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.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Ishihara R,Tatsuta M,Iishi H,Baba M,Uedo N,Higashino K,Mukai M,Ishiguro S,Kobayashi S,Murakami-Murofushi Kdoi
10.1002/ijc.20069keywords:
subject
Has Abstractpub_date
2004-06-10 00:00:00pages
188-93issue
2eissn
0020-7136issn
1097-0215journal_volume
110pub_type
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