6-ketoprostaglandin-f1-alpha and Carcinoma--Hepatocellular

Cyclooxygenase 2 (COX-2) has been suggested to be associated with liver carcinogenesis. Several reports have shown that NSAIDs inhibit the growth of hepatocellular carcinoma cell lines. There is little evidence of how COX-2 inhibitors regulate the proliferation of hepatocellular carcinoma cells or the mechanism involved. In our study, we investigated the growth-inhibitory mechanism of a selective COX-2 inhibitor, NS-398, in 4 hepatocellular carcinoma cell lines by studying cell growth, COX-2 and proliferating cell nuclear antigen (PCNA) expression, cell cycle distribution and the evidence of apoptosis. NS-398 inhibited the growth of all 4 cell lines in a time- and dose-dependent manner and the inhibitory effects were independent of the level of COX-2 protein expression. PCNA expression was downregulated by NS-398 in a dose-independent manner. NS-398 caused cell cycle arrest in the S phase with a reduction in cell numbers and cell accumulation in the G0/G1 phase, for all 4 cell lines. No evidence of apoptosis was observed in our present study. Our findings suggest that a selective COX-2 inhibitor might serve as an effective tool for the chemoprevention and treatment of hepatocellular carcinomas. A reduction in cell number in the S phase may be an important event in cell cycle arrest caused by NS-398 in hepatocellular carcinoma cell lines.

Topics: 6-Ketoprostaglandin F1 alpha; Antineoplastic Agents; Apoptosis; Carcinoma, Hepatocellular; Cell Cycle; Cell Division; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dinoprostone; G1 Phase; Humans; Isoenzymes; Liver Neoplasms; Membrane Proteins; Nitrobenzenes; Proliferating Cell Nuclear Antigen; Prostaglandin-Endoperoxide Synthases; Resting Phase, Cell Cycle; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; S Phase; Sulfonamides; Tumor Cells, Cultured

Eicosanoid production and the compositions of precursor fatty acids were determined in human cancerous and reference liver tissues. Seventeen hepatectomized cases (12 cases of hepatocellular carcinoma (HCC) and 5 cases of metastatic liver cancer) were evaluated. The cancerous tissues and the noncancerous reference tissues were separated, lipids were extracted, and the fatty acids were determined as methyl esters by gas chromatography. Prostanoids (6-keto PGF1 alpha and TXB2) were measured by radioimmunoassay. In HCC, the levels of alpha-linolenic acid (omega-3) (0.41 +/- 0.38 x 100 micrograms/g) and docosahexaenoic acid (10.41 +/- 4.96 x 100 micrograms/g) in liver cancer tissue were significantly less than those in the reference tissues. In HCC, the levels of TXB2 reference (1.86 +/- 2.77 pg/mg wet weight) and 6-keto PGF1 alpha were 10-fold higher than those in reference tissues. We speculate that in HCC higher prostanoid levels in the liver are related in part to tumor metabolism.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; alpha-Linolenic Acid; Carcinoma, Hepatocellular; Docosahexaenoic Acids; Eicosanoids; Fatty Acids; Female; Hepatectomy; Humans; Linolenic Acids; Liver Neoplasms; Male; Middle Aged; Thromboxane B2

In order to study the mechanism of cancer metastasis, AH100B cells, an ascitic hepatoma cell line, were transplanted into the small intestine of male Donryu rats. Each metastatic nodule in the liver was collected with the respective intestinal lesion. Each sample thus obtained was injected into the peritoneal cavity of male Donryu rats to make free cancer cells. Then, the cancer cells, having an intact cell surface, of the metastatic and primary intestinal lesion were collected respectively. After washing in Dolbecco's PBS (Ca2+ and Mg(2+)-free, pH 7.2), the definite numbers of cancer cells of the metastatic and primary intestinal lesion were incubated in the PBS containing [1-14C]-AA at 25 degrees C for 30 min, respectively. AA metabolites formed during the incubation period were extracted and subjected to TLC, followed by autoradiography. Each radioactive part was scraped off the plate and measured for its radioactivity. The pattern of the ability to synthesize PGs was different between the cancer cells which metastasized to the liver and those of the primary lesion, that is, percentage values of PGE2 and PGF2 alpha were higher (p < 0.01) in the cancer cells which metastasized to liver as compared with those of the primary intestinal lesion. These results suggest that PGs produced by hepatic metastatic cancer cells might play an important role in cancer metastasis.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acid; Carcinoma, Hepatocellular; Cell Line; Dinoprost; Dinoprostone; Intestinal Neoplasms; Liver Neoplasms; Male; Prostaglandin D2; Prostaglandins; Rats; Rats, Inbred Strains; Thromboxane B2; Tumor Cells, Cultured