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Screening And Analyzed The Clinicopathological Factors In Colorectal Cancer And Studies On Sauflsurea Involucrate Flavones Anti-cancer Activity In Colon Cancer Cell Lines

Posted on:2010-10-05Degree:MasterType:Thesis
Country:ChinaCandidate:F LvFull Text:PDF
GTID:2144360275998034Subject:Biochemistry and Molecular Biology
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As the prevalent malignancy of alimental track,the incidence and mortality for colorectal cancer graudually ascended in from the past years in China.The therapy for CRC most fails to hepatic metastasis.At present,the combination of multiple therapies plays a great role in CRC,especially surgical therapy.It's necessary to have a precise evaluation on the prognosis.However the clinical examinations can not meet with the request. Detection of the changes in the molecular level will assist in tumor therapy.One hundred and tewelve cases of advanced CRC with liver metastasis,and one hundred and three cases of advanced CRC without liver metastasis with a follow-up time for at least 5 years resection of the primary CRC were selected.Obvious positive expression difference was observed in haptoglobin(HP),osteopontin(OPN) and prostaglanbin I2 synthase(PTGIS) in the analysis of 7 molecular biomarkers by immunohistochemistry(IHC). HP,OPN and PTGIS were all found to be significantly higher in the case of CRC with liver metastasis than in case of non-metastasis CRC.Then we analyzed the clinicopathological factors and the expression of two biological factors,HP,OPN and PTGIS,respectively.HP either alone or with OPN,PTGIS and seminal vesicle invasion,was a significant variable in predicting the probability of liver metastasis. HP,OPN and PTGIS staining predicted metastasis risk with sensitivity (78.6%; 84.3%) and specificity (83%; 85.2%). So the differences in gene expression between colorectal tumors and paried liver metastasis CRC tumor may play a role screening the metastasis biomarkers.Chinese medicine can improve cancer patients'prognosis after surgical therapy and improve the patients'physical condition. The importance of genetic mutations in cancer has long been recognized,and the role of epigenetic modification has been suggested more recently.Natural plant active component play an essential role in human health,and may exert anti-cancer activities via epigenetic modulation. Investigation the effects of the flavones of Sauflsurea involucrate on the activity of DNA methylase indicate that the flavones can inhibit activity of M.Aluâ… . Cell proliferation studied by CCK-8 methods show that the natural flavones of Sauflsurea involucrata can inhibit cell growth with dose- and time-dependent manner. RT-PCR detection reveals that the DNA hypermethylation-related silencing gene of p16 in human esophageal squamous cell carcinoma cell line kyse510 can be reactivate by flavones. And cell circle analysis by flow cytometry,shows an effect on cell circle accumulation. Genome digestion show cancer cells treated with flavones which can be digested by Mspâ… ,but not Hpaâ…¡,suggesting that flavones is attributed to genomic instability promoted by genome-wide hypomethylation. On the basis of this analysis,for the practical application of flavones in the prevention of cancer,it may cause a moderate inhibition of the activity of DNA methylase and genomic instability.Our results report herein that the flavones can inhibit cancer cell growth,the potential mechanisms are reversal of hypermethylation and reactivation of epigenetic silence gene.These results suggest that Sauflsurea involucrata derived natural flavones may exert anti-cancer activities via epigenetic modulation and have been shown the potential use of flavones for the prevention carcinogenesis.
Keywords/Search Tags:hepatic matastasis of colorectal cancer, molecular biomarkers, flavones, cell proliferation, the activity of DNA methylase
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