Font Size: a A A

The Anti-tumor Molecular Mechanisms Of Interferon α On MHCC97 Cells

Posted on:2005-02-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:W Z WuFull Text:PDF
GTID:1104360125967424Subject:Oncology
Abstract/Summary:PDF Full Text Request
Human hepatocellular carcinoma (HCC) is one of the most common malignancies in Asia and African. It is estimated to 315, 000 new cases worldwide in every year. HCC has ranked the second major cause of cancer mortality in China. Due to the advance of diagnostic techniques and its therapeutic methods in the past several decades, the survival rate of HCC has been greatly improved and a long-term survival after HCC surgical resection is feasible as well. Albeit its excited therapeutic outcome, about 50%-60% of HCC patients die from tumor recurrence and metastasis even after curative resection. So researches on anti-metastatic strategies of HCC will still be the most difficult project and hotspot in the near future. Recently years, we tried to reduce tumor recurrence and metastasis in MHCC97 xenograft in nude mice and in clinical HCC patients?after resection?with IFN ? treatment and found a new anti-tumor phenomenon of IFN ? which was able to inhibit LCI-20D growth and metastasis in nude mice via its anti-angiogenic effects, but not via its anti-proliferative effects. We carried on this study as a continuous work of our previous one and expected to elucidate its anti-tumor molecular mechanisms on HCC more thoroughly by using MHCC97 cells in vitro. It would be helpful in HCC patients' selection and in providing prognastic marker of anti-metastatic clinical trial of IFN (. Section I: Identifing the differentially expressed genes in MHCC97 cells pre- and post- IFN ( treatmentAnalysis of the differentially expressed genes:Metastatic model of human hepatocellular carcinoma in nude mice (LCI-20D) was firstly established via orthotopic implantation in our institute. MHCC97 cell line which originated from LCI-20D with higher metastatic potential was established by means of alternating cell culture in vitro and growth in nude mice. This cell line remained some characteristics of HCC such as HBVs antigen expression and AFP serection. Furthermore it was an ideal model in vitro for the study of experimental intervetion of HCC recurrence and metastasis because of its higher metastatic rate in nude mice. IFN ( is known as a multiple functional cytokine which exert antiviral, antiproliferative, antiangiogenic, proapoptotic and immunomodulatory activities. On the basis of these background, we first identified differentially expressed genes with high-through cDNA microarray in MHCC97 cells before or after treatment with 3,000 IU/ml IFN (. A total of 211 differentially expressed genes was identified in tested 8464 human genes. Among them, there were about 165 genes whose transcriptional activities were down-regulated by IFN (, while about 46 genes whose transcripitional activities were up-regulated by IFN (. Those differentially expressed genes might be divided into nine clusters according to their biological functions. They were 1) genes encoding proteins and enzymes whose functions were related to material and energy metabolisms; 2) genes encoding proteins whose functions were related to cell proliferation, differentiation and apoptosis; 3) genes encoding proteins whose functions were related to cell morphogenesis, adhesion, tumor metastasis, and cytoskeleton remodeling; 4) genes encoding proteins whose functions were related to signaling transductions in multiple signaling pathways; 5) genes encoding proteins whose functions were related to tumor angiogenesis; 6) genes encoding proteins whose functions were related to transcriptional activities; 7) genes encoding proteins whose functions were related to mRNA, protein processing, secretory, proteolysis; 8) genes encoding proteins whose functions were related to antigen processing, growth factors and antivirus and 9) genes encoding proteins whose biological functions were not yet known. Above results did imply that IFN ( had complicated effects on MHCC97 cells.II. Verification of the differentially expressed genesTo confirm the results of cDNA microarray, we synthesized 10 pairs of the primers of the differentially expressed genes and analysed their mRNA e...
Keywords/Search Tags:Anti-tumor
PDF Full Text Request
Related items