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Effect Of GanZheng Solution On Signal Transduction Of Raf-MEK-ERK Activated By TGF α In SMMC-7721 Cells

Posted on:2003-02-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:F YinFull Text:PDF
GTID:1104360065450269Subject:Traditional Chinese Medicine
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Hepatocellular carcinoma(HCC), one of the ten most frequent cancers worldwide, is the third leading cause of cancer deaths in the world (450,000-1,000,000 deaths a year ) and the second leading cause of cancer deaths in China. About 43.7% patients of HCC in the world are Chinese. Most of them lose the opportunity of surgical resection when detected. Systemic chemotherapy is generally ineffective and is frequently associated with unacceptable mortality. The treatment of HCC remains difficult and challenging because in addition to the liver cancer, most patients with HCC have underlying chronic liver disease predisposing them to develop liver failure after surgery and chemotherapy. So most patients receive transcatheter arterial chemoembolization(TACE) , percutaneous ethanol injection(PEI), radiofrequency ablation(RFA) , focused ultrasound(FUS) or Chinese traditional medicine(TCM). According to the theory of TCM and clinical study over ten years, professor Yao Shukun had developed Ganzheng solution with the therapeutic principles of clearing away heat and toxic material , removing blood stasis and resolving lumps, strengthening the spleen and replenishing qi. Researches had proved that Ganzheng solution had obvious repressive effect on the genesis of HCC. The mechanisms of oncogene, antioncogene, anti-angiogenesis, apoptosis, cell cycle and immune function on Ganzheng solution had been investigated which showed the mult-targets and integral regulation of TCM.The regulation of cellular motiogenesis and proliferation under normal circumstances is dependent on a number of separate, yet integrated, signaling pathways responsible for the transmission of extracellular signals to the cell nucleus. The characteristic of HCC is that the normal growth-promoting and growth-arresting components of the signal transduction cascade becomes unbalanced, the net result of which leads to uncontrolled hepatocyte proliferation. Mitogen activated protein kinases(MAPKs) are activated in response to external stimuity in numerous cell types. Activation of the MAPK cascade plays a central role in many signal transduction pathways. MAPK phosphorylates and regulates numerous cellular proteins including growth factor receptors, transcriptional factors, cytoskeletal proteins, phospholipases and other protein kinases. In addition they are a convergence point essential to transmitting mitogenic and proliferative signals. As the final intermediate in the cascade, ERK transverses the nuclear membrane resulting in the subsequent activation of oncogenes including c-fos, c-jun through regulation of transcription.This study is to investigate the repressive effect of GanZheng solution on the genesis of HCC induced by diethylnitrosamine (DEN) in rats and the effect of GanZheng solution on the Raf-MEK-ERK of SMMC-7721 cells induced by Transforming growth factor a (TGF a).1. Effect of GanZheng solution on ERK in Hepatocellular carcinoma of ratsThis study was to investigate the repressive effect of GanZheng solution on the genesis of HCC induced by DEN in rats and the effect of GanZheng solution on ERK, using matrine as control.75 male rats were randomly divided into four groups, i.e., normal control group (group A, n=15), pathologic control group (group B, n=20), GanZheng solution group (group C, n=20) and matrine group (group D, n=20). The experimental period was 20 weeks. Except for normal control group, rats of other three groups were fed with DEN solution 35mg/kg twice a week for 16 weeks and preventive drugs were used everyday for 20 weeks. DEN was terminated in all groups after 16 weeks and all rats were sacrificed at 12th, 20th experimental weeks respectively. The histological change in liver tissue were observed by Hematoxylin-eosin(HE) staining. Histochemistry of Y -glutamyl transpeptidase(GGT)positive foci were observed at 12th experimental weeks. ERK expression in liver tissue by iummnohistochemistry (IHC) staining was observed to compare the effect of matrine. The results were as follows:(1) At 12th experimental...
Keywords/Search Tags:Ganzheng Solution, Hepatocellular carcinoma(HCC), signal transduction, Transforming growth factor α(TGF α), Raf-MEK-ERK, Serapharmacological study
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