Study Of The Inhibition Function Of FHIT Gene On Hepatocellular Carcinoma And Its Mechanisms

Primary Hepatocellular carcinoma (PHCC) is one of the most common malignant tumors in China. Its morbidity and mortality rank the 3rd and 2nd respectively among all types of malignant rumors. Moreover, they tend to be increasing in recent years. PHCC is characteristic of quick development, early metastasis, bad prognosis and short survival time. Traditional surgery therapy, radiotherapy, chemotherapy and combination of TCM and western medicine are not so good ultimately. With the development of tumor's biological therapy, new methods such as gene therapy for PHCC were studied and preliminary effect was showed up.FHIT gene is a new tumor suppressor gene found in 1996, which is closely related with the genesis of tumor. Since FHIT gene has been investigated extensively in many human epithelial cancers, such as lung small cell carcinoma, head and neck squamous cell carcinoma, cervical, breast, digestive tract cancers, etc., and in related cell lines. The abnormal transcription and homozygous loss oralleles was observed in most cancers. However, the mechanism of FHIT gene is still unkown. Therefore, deep study of FHIT gene is of great significance to clarify the cause of HCC and help the prevention and cure of this disease.The purpose of this study is to investigate the relationship between the expression of FHIT gene and PHCC development and malignancy, and elucidate the effect of FHIT on cell cycle and apoptosis regulation in hepatocellular carcinoma cells, so as to provide the experimental data and academic foundations on genetherapy of HCC. The main research findings of this study are categorized as follows:l.The expressions of FHIT and Ki-67 antigen in 70 cases of human Hepatocellular carcinoma ,10 cases of para-neoplastic liver tissue and 10 cases of normal liver tissue detected by immunohistochemistry staining (SP method). (l)The difference of FHIT expression between carcinoma and normal or para-neoplastic liver tissue was highly significant P<0.05). (2)The expression level of FHIT gene was closely related to histological classification and the invasiveness in HCC(P<0.05). The Ki-67 antigen were significantly correlated with histological grades,clinical stages and the invasiveness of HCC(P <0.05).The loss expression of FHIT was closely correlated with Ki-67 antigen. Conclusion: FHIT gene may play a role in the regulation of proliferation of hepatocellular carcinoma. And reduction of FHIT gene expression may be related to the pathogenesis and development of in HCC.2. Construct eukaryotic expression vector of FHIT for explo- ring the roles of FHIT gene in the carcinogenesis of hepatocellular carcinoma. The sequence analysis reveals that pcDNA3.I-FHIT is 100% homologous to data published in GeneBank. The construction of the recombinant plasmid pcDNA3.1-FHIT will be helpful in the further study of hepatocellular carcinoma.