The expression of c-kit and proliferating cell nuclear antigen in oval cells of rats with hepatocellular carcinoma

摘要

OBJECTIVE: To study the relationship between oval cells and primary hepatocarcinoma and theexpression of c-kit and proliferating cell nuclear antigen (PCNA) in oval cells of rats with hepatocellularcarcinoma.METHODS: A hundred and twenty clean SD rats were divided into three groups: normal group,cancer-induction group and intervention group. The normal group was fed with standard forage while therest two groups were fed with 3’-methyl-2-methylamino-azobenzene (DAB) to induce carcinoma for 14weeks and then fed with standard forage and water. Uscharidin was injected abdominally to theintervention group from the first week to the 14th week. All rats were killed and biopsy specimens weretaken from the left and right liver lobes for immunohistochemical staining of c-kit and PCNA on the 2nd,4th, 6th, 8th, 10th, 12th, 14th, 16th, 18th, 20th, 22nd, and 24th week.RESULTS: From the 2nd to 14th week after liver infection, c-kit positive cells, mainly oval cells werefound in the portal area in the carcinoma-induction group and dotted positive pigmentations in liverlobules. In the 22nd week, a large number of cancerous nodes occurred and nuclei heteromorphi-m wasapparent; the number of positive cell decreased but positive cells could be sparsely observed in cancerousnodes. In the 2nd week of the carcinoma-induction process, PCNA positive cells were oval cells in theportal area. In the 4th week, a lot of hepatic cells were positively stained, especially in the central veinarea. In the 6th week, PCNA positive cells could be seen in the lobules of the liver. In the 8th week, thenumber of PCNA cells decreased comparatively. From the 10th to 14th week, oval cells in the portal areawere still over-expressed. From the 16th to 24th week, a large number of cancerous nodes occurred andPCNA was over-expressed in some of them. In necrotic cancerous nodes, the para-cancerous PCNApositive cells were sparsely distributed and their number was less than that of PCNA positive cells ofcancerous tissues.CONCLUSIONS: Hepatic stem cells originating from the terminal biliary plexus of the portal area areinvolved in the development of hepatocarcinoma because c-kit positive cells expressed in cancerousnodes, accompany the whole process of the development. In the middle inflammatory period ofcarcinoma-induction, the expression of PCNA in hepatic cells peaked, but the index decreased in the lateinflammatory period and in the proliferated fibrosis stage. The expression of PCNA is a tortuous process,going up, down, then up again from normal tissues to cancerous tissues. Combined with pathologicalfindings, PCNA can be considered as a warning index for carcinomatous cells.