Enhancement of colon carcinogenesis by prostaglandin E2 administration.
Although an accumulating body of evidence indicates that levels of prostaglandin E(2) (PGE(2)) in human and rodent colon cancers are higher than those in surrounding normal tissues, the precise contribution of PGE(2) to the process of colon cancer development has still been unclear. Therefore, we designed a study using a well-established azoxymethane (AOM)-induced colon carcinogenesis in male F344 rat model to investigate whether administration of exogenous PGE(2) has a real impact on colon carcinogenesis. Intraperitoneal PGE(2) injections (7.7 micro g) once a week for 25 weeks significantly increased the AOM-induced colon tumor incidence (percent rats with tumors, 92 versus 53%, P < 0.05), especially adenocarcinomas (92 versus 47%, P < 0.05), and multiplicity (number of tumors per rat, 2.8 versus 1.0, P < 0.05). PGE(2) treatment significantly increased 5-bromo-2'-deoxyuridine (BrdUrd) labeling index (11.8 versus 9.7%, P < 0.05) and reduced apoptotic index (0.34 versus 0.53%, P < 0.05) in colon cancers induced by AOM. PGE(2) exhibits its physiological functions through binding to E-prostanoid (EP) membrane receptors EP(1-4). All four types of EP receptors were detected in AOM-induced colon cancers using reverse transcription-polymerase chain reaction (RT-PCR). Our results provide evidence that PGE(2) enhances colon carcinogenesis through induction of cell proliferation and reduction of apoptosis.
Kawamori
Toshihiko
T
Cancer Prevention Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
Uchiya
Naoaki
N
Sugimura
Takashi
T
Wakabayashi
Keiji
K
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane / Q000633:toxicity; D001973:Bromodeoxyuridine; D002273:Carcinogens / Q000633:toxicity; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D015232:Dinoprostone / Q000008:administration & dosage* / Q000097:blood; D018450:Disease Progression; D015994:Incidence; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002273:Carcinogens; D017931:DNA Primers; D018078:Receptors, Prostaglandin E; D001973:Bromodeoxyuridine; D015232:Dinoprostone; D001397:Azoxymethane