1.The Role Of STAT3 On The Proliferation And Migration Of Human Liver Carcinoma Cell Line Under The Stimulation Of IL-6 Cytokine 2.The Study Of 5-Fu+ Focused Ultrasound Surgery On Curing Ileocecal Tumor In Mouse Model

Hepatocellular carcinoma(HCC) is the primary maliganant tumor in the human liver, but the molecular mechanisms leading to liver cell transformation remain largely unknown. Cytokines evoke signal through binding to their receptors. IL-6 cytokine is thought as a major immunity regulator, whose signal is intermediatal by two signaling pathways :Jak/Stat pathway and Ras/MAPK pathway. STAT(signal transducer and activator of transcription) proteins were found as mediators of cytokine signaling in mammals which contain three conserved domains: a DNA binding domain, an SH2 domain, an SH3 domain and a site of tyrosine phosphorylation. STAT participate in a wide variety of physiological processes and even directs contradictory responses.Adenoviral vectors have recently played an important role in gene transfer technology. There are many advantages in using Ad vector. As eukaryotic gene expression vector, Ad can accommodate up to 7. 5 kb of foreign DNA and replicate efficiently to high titers. It remains epichromosomal in all know cells and therefore dose not interfere with other host genes. The application of Ad vectors in cancer gene therapy have been demonstrated to be effective in carrying tumor suppression gene. These features make it the best-suited vector system for gene therapyapplications.In this paper, we constructed two adenoviral vectors carrying wild type StatS(StatSWT) and dominant negative StatS(StatSCYF). The correct expression and activation of STAT3WT and STAT3CYF were examined in hepatoma cells with anti~STAT3 and anti-phospho-STAT3 antibody. The dominant negative StatS cause a reduction of the tyrosine phosphorylation of wild type StatS and forms a non-functional weak heterodimer with activated StatS, which prevent activated StatS translocating to the nucleus, binding to DNA response elements and activating target gene transcription.To observe the effects of STATS on the proliferation and migration of human liver carcinoma cell line BEL-7402 in vitro, the cells were infected with Adi. StatSWT and Adl.StatSCYF virus to overexpress STAT3WT and STAT3CYF. Wound assay results indicated that STAT3WT inhibited the migration of BEL-7402 cell. But transfection of Adl.StatSCYF impaired this inhibition. MTT studies demonstrated that STATS did not effect BEL-7402 cell growth.There were always different opinions about the effect of IL-6 cytokin on cell growth in different cells. To examine its effect on BEL-7402, MTT and Wound assay method were also carried out to examine the effect of IL-6 cytokin on the proliferation and migration of BEL-7402 cell. The result showed that IL-6 cytokin plays a critical role in BEL-7402 cell migration. But cell migration was inhibited by overexpression of STAT3WT under the stimulation of IL-6 cytokine. These finding suggest that increasing migration of BEL-7402 cell in response to IL-6 cytokin was not dependent on STATS activition. May be there was some other signaling pathway which mediates the effect of IL-6 cytokin on BEL-7402 cell migration. Thus the increase or decreasing of BEL-7402 cell migration relayed on the balance of two signaling pathway. MTT studies alsodemonstrated that IL-6 cytokin did not effect BEL-7402 cell growth.