Anti-tumor effects of cimetidine on hepatocellular carcinomas in diethylnitrosamine-treated rats.
Cimetidine is known to have an anti-tumor effect on certain types of malignancies, though on hepatocellular carcinomas (HCCs), its effect remains unclear. We studied the anti-tumor effects of cimetidine on chemically-induced HCCs in rats. Four-week-old male Wistar rats (n=105) were divided into 4 groups. Those in groups A and B were administered diethylnitrosamine (DEN) intraperitoneally at 100 mg/kg body weight every week for 6 weeks, during which rats in group A were given tap water and those in group B received cimetidine (100 mg/kg/day) in their drinking water. Rats in groups C and D were administered saline instead of DEN and given tap water with 100 mg/kg/day of cimetidine, respectively. The animals were sacrificed at 7, 12, 22 and 32 weeks after the first administration of drugs and examined. Liver nodules were observed only in groups A and B, with the number of nodules, maximum diameter of the largest nodule, and liver weight significantly lower in group B. Immunohistochemistry findings showed that glutathione S-transferase placental-positive preneoplastic foci were significantly decreased in group B. Cimetidine treatment decreased the number of proliferating cell nuclear antigen-positive hepatocytes and tended to enhance natural killer (NK) cell activity in splenic lymphocytes. In addition, flow cytometry revealed that the proportion of NK cells among total splenic lymphocytes was not affected by cimetidine treatment. Our results showed that cimetidine has an inhibiting effect on hepatocarcinogenesis.
Furuta
Koichiro
K
Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, Japan. furuta@med.shimane-u.ac.jp
Sato
Shuichi
S
Miyake
Tatsuya
T
Okamoto
Eisuke
E
Ishine
Junichi
J
Ishihara
Shunji
S
Amano
Yuji
Y
Adachi
Kyoichi
K
Kinoshita
Yoshikazu
Y
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002927:Cimetidine / Q000494:pharmacology* / Q000627:therapeutic use; D004052:Diethylnitrosamine / Q000633:toxicity; D022781:Hepatocytes / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar
D016588:Anticarcinogenic Agents; D004052:Diethylnitrosamine; D002927:Cimetidine