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The Studies The Effect Of Mycophenolate Mofetil On Human Hepatoma Carcinoma Cell HepG-2 Cells

Posted on:2009-09-15Degree:MasterType:Thesis
Country:ChinaCandidate:Y LiuFull Text:PDF
GTID:2144360245498444Subject:Surgery
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Hepatocellular carcinoma (HCC) is one of the most malignant diseases and has become increasingly important all over the world. HCC is currently the fifth most common solid tumor worldwide and the fourth leading cause of cancer-related death. Therefore, it is a permanent subject to find new methods for the treatment of HCC. There are many methods in the treatment of HCC such as chemotherapy by using new antitumor drugs, operation, intervene therapy, liver transplantation, and so on. Among these methods, liver transplantation has now been considered one of the most curative treatment options for HCC. It is reported that the current 1- and 5-year survival rates for HCC patients undergoing orthotopic liver transplantation are 77.0% and 61.1%, respectively, and the 5-year survival rate has steadily improved from 25.3% in 1987 to 61.1% during the most recent period studied . Though liver transplantation is an effective method nowadays in the treatment of HCC, there is still a certain recurrence after liver transplantation.Patients who receive chronic immunosuppression following organ allotransplantation display an increased incidence of de novo neoplasms. Studies have identified definite risk factors for malignancy: namely, aging, and the quantity/quality of the administered immunosuppressive drugs. Mycophenolate mofetil (MMF) is a potent, reversible, noncompetitive inhibitor of eukaryotic inosine monophosphate dehydrogenase (IMPDH). Mycophenolate mofetil inhibited T- and B-cell proliferation because MMF tend to depend on the denovo pathway for synthesis of guanosine nucleotides. Mycophenolic acid has antiproliferative activity in vitro against a variety of tumor-cell lines and in vivo against murine leukemias, lymphomas, and solid tumors. A serious concern is whether the increased power of immunosuppressive combinations administered to organ transplant patients has now led to an increased risk for developing tumors. In order to realize the roles of Mycophenolate mofetil in hepatocellular carcinoma cells and possible clinical application of Mycophenolate mofetil in hepatocellular carcinoma therapy, we examined the anti-proliferation effects of Mycophenolate mofetil on hepatocellular carcinoma cells in vitro.objective To investigate the effect of cell growth, cell adhesion and apoptosis of mycophenolate on Human Hepatocellular Carcinoma HepG-2 Cells. Methods Different concentration of mycophenolate were given into the cultured HepG-2 cells in vitro. The inhibition ration of cell viability was assessed by MTT assay, cell apoptosis was observed using Hoechst33258 staining, cell cycle was tested with flow cytometry, The cell adhesion were investigated by in vitro adhesion assay. Results mycophenolate could inhibit the growth HepG-2 cells and cause apoptosis, mycophenolate inhibited the adhesion in a concentrations-dependent manner. Marked morphological change of cell apoptosis was observed by Hoechst 33258 staining, mycophenolate could decrease the S phase proportion and increase the G0/GI phase proportion in cell cycle by flow cytometry. [3H]-thymidine uptake people found that the use of different concentration are on cell proliferation significantly inhibited, Rt-pcr through the experimental study of different drug concentration effects on the liver cancer cells 72 hours ICAM-1,VCAM-1 gene expression, Genetic expression of ICAM-1,VCAM-1 decreased as the drug concentration increased.mycophenolate mofetil has remarkable effect of inhibition on the growth HepG-2 cells conclusion mycophenolate has remarkable effect of inhibition on the growth HepG-2 cells.ConclusionHepatocellular cancer (HCC) is the fifth most common solid tumor worldwide, accounting for 500,000 new cases annually. A majority of patients present with advanced disease. Despite recent advance in understanding the molecular biology of hepatocellular carcinoma cells and the induction of some new chemotherapeutic agents for the treatment of this malignant disease, there are few efficient therapeutic measures or regimes especially for the patients who are in the mid- or final stages, and the dismal survival rate has not changed too much for this leading cause of cancer deaths in the world. It was reported that over 60% of patients with HCC, treatment is complicated by underlying disease such as liver cirrhosis, hepatic dysfunction and so. New approaches targeting molecular abnormalities specific to HCC are needed to improve patient outcome.Therefore, it is a permanent subject to find new and effective curative methods for the clinical treatment of hepatocellular carcinoma in the future.Mycophenolate mofetil (Cellcept; Roche, Nutley, New Jersey, USA) is an antimetabolite that has an increasing role in the treatment of autoimmune disease and the prevention of solid organ transplant rejection. It is the prodrug for mycophenolic acid, which prevents replication of T and B lymphocytes by selectively inhibiting inosine-5-monophosphate dehydrogenase and consequent de novo purine synthesis, and also immune trafficking through the inhibition of vascular endothelial adhesion molecule expression. Initial evidence for MMF's efficacy in animal models of ocular inflammation led to early reports of its success for the treatment of refractory human disease, with subsequent case series supporting its use in noninfectious uveitis.In this study, we educed that mycophenolate mofetil could inhibit the growth HepG-2 cells and cause apoptosis, mycophenolate mofetil inhibited the adhesion and cell proliferation in a concentra- tions-dependent manner. Genetic expression of ICAM-1,VCAM-1 decreased as the drug concentration increased. Marked morphological change of cell apoptosis was observed by Hoechst 33258 staining, mycophenolate mofetil could decrease the S phase proportion and increase the G0/GI phase proportion in cell cycle by flow cytometry. Through [3H]-thymidine uptake people found that the use of different concentration are on cell proliferation significantly inhibited, Rt-pcr through the experimental study of different drug concentration effects on the liver cancer cells 72 hours ICAM-1,VCAM-1 gene expression, Genetic expression of ICAM-1,VCAM-1 decreased as the drug concentration increased.mycophenolate mofetil has remarkable effect of inhibition on the growth HepG-2 cells.
Keywords/Search Tags:mycophenolate mofetil, Hepatoma carcinoma cell, Carcinoma, apoptosis, cell cycle invasiveness
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