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Experimental Study On The Apoptosis Regulation Of TGF-β1 In Human Lung Adenocarcinoma

Posted on:2007-11-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:B DengFull Text:PDF
GTID:1104360185970408Subject:Surgery
Abstract/Summary:PDF Full Text Request
TGF-β1 belongs to super family of growth factor and its biological effect is very common including regulation of cell proliferation and differentiation, regulation of embryonic development, enhancement of ECM formation and suppression of immune- system. TGF-β1 is highly expressed in many malignant tumor cells including lung cancer cells and it can be expressed in matrix cells around cancer cells. In current opinion, TGF-β1 suppresses proto-oncogene such as c-myc to inhibit cell growth cycle of G1 stage to S stage.But in the middle or later stage of cancer when the tumor infiltrating blood vessels has been forming, TGF-β1 can make tumor cells be of much maliganancy by stimulation of tumor infiltrating blood vessls, by enhancement of cell migration and by immune suppressing.So the microenvironment of growth, infiltration and metastasis for cancer cells is forming. According to the results of observation in normal cells, TGF-β1 can regulate Fas/FasL. Fas/FasL system is a very important apopatosis pathway. In normal cells, TGF-β1 can upregulat Fas, so that caspases in Fas/FasL pathway are activated to induce cell apoptosis. Moreover, caspases can be activated by combination of Fas with FasL. So TGF-β1 can be regarded as an important factor that induces apoptosis and plays the role of abnormal cell clearance.But the relationship between TGF-β1 and cancer cell apoptosis is not very clear yet. The experimental report on it is very scarce.In order to study the relationship of TGF-β1 and cancer apoptosis,the experiment develops according to three steps: step1,siRNA target sequences were analysed and synthesized by siRNA design software plus Angela siRNA principle.Then siRNA vehicle was reformed by the inserting of siRNA target sequences to PAVU6+27. Expressing Level of TGF-β1 was analysed with indirect immunofluorescence and western blotting after siRNA vehicles were transfected into A549 cells. Step2, the expression level of Fas/FasL and activity of caspase-3/caspase-8 was detected in A549 cells that had been transfected with pOligo1216 or pOligo Control. Then the expression level of Fas/FasL and activity of...
Keywords/Search Tags:Lung adenocarcinoma, TGF-β1, TGF-β1 receptor, RNA interference, Fas/FasL, apoptosis, stable transfection, tumor specific T lymphocytes
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