Expression And Significance Of IL-2, SIL-2R, IL-4, IGF-Ⅱ, IGF-ⅡR And BFGF During Hepatocarcinogenesis In Rats

In order to provide an experimental basis for early diagnosis and cytokine therapy on HCC (hepatocellular carcinoma), the expressions of IL-2, sIL-2R, IL-4, bFGF, IGF-Ⅱ, IGF-ⅡR during hepatocarcinogenesis in rats were studied. Experi- mental hepatocellular carcinomas were induced with the administration of diethylnitrosamine (DEN) in Wistar rats. The serum levels of IL-2, sIL-2R, IL-4 and bFGF were detected by enzyme linked immunosorbent assay (ELISA). Im- munohistochemical staining method was used for measuring the expressions of IGF-Ⅱand IGF-ⅡR in liver tissues in the carcinogenic successive stages. The serum level of IGF-Ⅱwas detected by radioimmunoassay (RIA). In this study, we found that: 1. 70.6% (36/51) hepatocellular carcinoma were induced by DEN. The procession of hepatocarcinogenesis in this model included three stages—hepatic toxic lesion, hepatic proliferation/cirrhosis and hepatic carcinogenesis. This ex- perimental hepatocarcinoma rat model induced by DEN is similar with the human hepatocellular carcinoma not only in forming procession but also in morphologic features. 2. The serum level of IL-2 was decreased in association with progression of HCC, it was higher in HCC group than that in control group, hepatic lesion group and proliferation/cirrhosis group. 3. There were no significant differences among all groups in the serum level of sIL-2R. 4. The serum level of IL-4 was significantly lower in proliferation/cirrhosis group than that in control group and hepatic lesion group, and it was lower in HCC group than those in other groups. 5. The IGF-Ⅱpresent an pattern of "high-low-high" in terms of degree of expression not only in liver tissues but also in serum during carcinogenesis.The expressions of IGF-Ⅱand IGF-ⅡR in HCC were lower than those in the paratumor foci, para- tumor hyperplastic nodules and paratumor atypical hyperplastic nodules. 6. The serum level of bFGF changed mainly in the stage of hepatic carcinogenesis, it was lower in HCC group than those in other groups. There was no correlation between bFGF and IGF-Ⅱ. It may be concluded that: 1. The liver cancer model induced by low dose DEN is an ideal experimental model for the study of hepatocarcino- genesis. 2. Measuring the serum level of IL-2 can monitor the pathogenetic condition and systematic immunologic status. The serum level of IL-2 is a sensitive index to early hepatocarcinogenesis. 3. Th1/Th2 cytokine imbalance is not observed. 4. IGF-Ⅱmight be associated with hepatocytic proliferation and malignant transformation of hepatocytes. Once tumours formed, probably it was not an important regulatory factor any longer. 5. The essential role of IGF-Ⅱat the immediate initiation stage of carcinogenesis can not be ignored. Thus this expression can be used as a suitable marker for early detection of the cancerous process. 6. The two angiogenic growth factors, bFGF and IGF-Ⅱ, have no synergistic effect in the carcinogenesis and progression of HCC.