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Studies On Anti-tumor Effects Of Pseudolaric Acid B And Its Mechanism

Posted on:2010-09-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:A G MengFull Text:PDF
GTID:1114360275469401Subject:Biochemistry and Molecular Biology
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Pseudolarix acid B is a natural diterpenoid compound isolated from the root bark of P. kaempferi Gordon, and displays antifungal, antifertil, antivascular and antiangiogenic properties. Previous studies have shown that pseudolarix acid B displays antiangiogenic properties in a variety of cancer cell lines including gastric carcinoma, liver, breast, colon, cervical, protate cancer and melanoma cell, and accompanied with up–regulation of p53, but the underlying mechanism has not been fully elucidated.The aim of this study was to investigate the mechanism of PLAB–antitumor in wild–type p53 and mutant–type p53 tumor cells. Since p53 mutations are often observed in human gastric carcinoma cells and rarely in melanoma cells, these kinds of cells are representative as cell line models. Firstly, we studied the antitumor effect of Pseudolarix acid B on various human tumor cells. Furthermore, we investigated PLAB mechanism of action using MGC803(mtp53), AGS(wtp53) and SK–28(wtp53) as representative cell line models, which is foundation that PLAB may be a promising chemopreventive agent anti-angiogenic properties.PartⅠAntitumor effect of Pseudolarix acid B on various human tumor cellsObjective: To evaluate the antitumor effect of PLAB on various human tumor lines in vitro, and further investigate mechanism of PLAB as a representative cell line model.Methods: The expression of PPARγwas detected by RT–PCR; the role of different concentration of PLAB on cell growth was tested by MTT in vitro.Results: 1. PLAB had a potent inhibitory effect on the growth of MGC803,AGS and SMMC7721 cells in a dose–dependent and time-dependent manner (P< 0.05), and the order of the concentration of 50% cytotoxicity (IC50) against the various human cancer cell lines for 48h was AGS (0.89μmol/L)
Keywords/Search Tags:Pseudolaric acid B, apoptosis, Fas/APO–1, caspase–3, Bcl–2, Bax, PPARγ, cell cycle arrest, Cdc2, p53, Chk2, ATM
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