Experimental Studies On The Gene Therapy Of Hepatocellular Carcinoma By Adenovirus-delivered SiRNA Targeting C-Met

Hepatocellular Carcinoma (HCC) is the fourth most common cause of death from cancer, and China alone accounts for 53% of all liver cancer deaths worldwide. With the expectation of increasing therapeutic efficacy, gene therapy is being investigated as a new treatment modality. c-Met is a transmembrane tyrosine kinase receptor for hepatocyte growth factor/scatter factor which has been considered a very important target molecule for cancer therapy since it plays a pivotal role in tumorigenesis. In this study, we detected that c-Met expression is elevated in about 45% of HCC patient samples in China, we also found that c-Met protein level is 7-8 fold higher in MHCC97-L and HCCLM3 HCC cell lines than in the LO2 (a normal human liver cell line), BEL7402, SMMC7721 and HepG2 HCC cell lines. Furthermore, c-Met was tyrosine autophosphorylated in MHCC97-L and HCCLM3 cells even without HGF stimulation. and consequently we hypothesized that overexpression of c-Met may be associated with hepatocarcinogenesis and knockdown of c-Met may inhibit tumorigenic growth and invasion of HCC whose c-Met is overexpressed.RNA interference is a newly-developed technique to knock down the specific gene expression and has potential application in cancer gene therapy studies. Several vectors have been developed to deliver siRNA. Advantages such as the availability of high virus titer, infection of a broad spectrum of cell types and independence on active...