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Histone Acetylation Dads In Vitro And In Vivo Differentiation Of Human Gastric Cancer Cells Induced By

Posted on:2006-06-08Degree:MasterType:Thesis
Country:ChinaCandidate:S L XiangFull Text:PDF
GTID:2204360155461818Subject:Pathology and pathophysiology
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Objective: This part is to investigate the change of histone acetylation level and regulated expression of p21WAF1 protein in the differentiation induced by diallyl disulfide (DADS) on human gastric cancer MGC803 cells.Methods: Cell morphology was observed by inversion microscope and optics microscope. Western Blot which measured the histone acetylation and related protein p21WAF1 was analyzed to elucidate the possible mechanism of DADS induced MGC803 cells differentiation.Results: HE staining and morphometric analysis indicated the in enlarged cytoplasm, the reduced nuclear/cytoplasmic ratio in MGC803 cells after treated with DADS 24 h and the cell atypia significantly decreased. By western blot, the acetylation level of histone H3 in MGC803 cells was elevated after treated by DADS 6h, and the maximum effect was higher 38% than untreated cells at 24h. At the same time, the expression of p21WAF1 also is increased. But the acetylation level of histone H4 did not changed.Conclusion:1. The enhanced acetylation level of histone H3 appeared is important mechanismsby which DADS induced MGC803 cells differentiation.2. DADS induce MGC803 cells differentiation accompany with the expression increasing of p21WAF1 protein.Objective: This part is to observe the effects of DADS, which induces the differentiation of gastric adenocarcinoma cells, and the influence of histone acetylation of human gastric cancer cells transplantable tumor.Methods: The molde were establishedly implanting the human gastric carcinoma MGC803 cells, which were untreated or treated with 30mg·L-1 DADS for 1 day, into the right axial regions of nude mice. The xenograft tumor growth in mice was observed after treated with DADS in vitro and intraperitoneal injection of DADS. The morphological changes of the tumors were examined under light microscopy. Phase distribution of xenograft tumor cells cycle was analyzed by flow cytometry(FCM). Expression of proliferating cell nuclear antigenp21WAF1and acetylation of histone H3, H4 in every group xenograft tumor was determined by Western Blot analysis.Results: No xenograft tumor generation on nude mice when MGC803 cells treatment with DADS(30mg·L-1) in vitro. When the dose of DADS were 50 mg·kg-1 , 100 mg·kg-1 and 200 mg·kg-1, the tumor growth was significant inhibition the inhibiting rates on tumor were 27.8% , 66.1% and 73.0 %, and inhibition expression of PCNA protein in implanted tumor. Cells density and heteromorphism diminutus after treated with DADS. Flow cytometry analysis revealed that treating xenograft tumor cells with increasing quantities of DADS increased the percentage of cells in the G2/M phase. The proportion of xenograft tumor cells in the G2/M phase after treatment with 100mg·kg-1, 200mg·kg-1DADS, more than 2.22 and 3.37 times that occurring in NS group. Western blot analysis...
Keywords/Search Tags:anti-proliferation, differentiation induction, histone acetylation, diallyl disulfide, stomach neoplasm, p21WAF1
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