ABSTRACT
OBJECTIVE To explore the anti-atherosclerotic effect of the extract of traditional Chinese medicine formula Dan-yi-lian(DYL)and the related mechanism.METHODS Atherosclerosis(AS)mod-el was established in ApoE(-/-)mice with a western diet. The mice were orally administered with differ-ent doses of DYL or vehicle daily for 28 d.The anti-atherosclerotic effect was evaluated by measuring the aortic atherosclerotic lesion area and media thickness with ultrasound imaging and histological sec-tions staining method. The effect on blood lipid was investigated by determining TC, TG, LDL, HDL, Apo-A1, Apo-B, etc. The anti-oxidative activity as assessed by determining the level of SOD, CAT, GSH,GSH-Px and MDA.Western blot analysis was used to determine the effect on ICAM-1,VCAM-1, MMP-2 and TNF-α. RESULTS In Dan-yi-lian administered ApoE(-/-)mice,the plaque area and media thickness were significantly reduced. Meanwhile, serum TC, TG, LDL and Apo-B were decreased, in contrast to the increased level of HDL and Apo-A1.On the other hand,SOD,CAT,GSH and GSH-Px were increased, while MDA was reduced in liver homogenate. In addition, the expression of ICAM-1, VCAM-1,MMP-2 and TNF-α was obviously inhibited by Dan-yi-lian.CONCLUSION Dan-yi-lian exhibit-ed potent anti-athero-sclerotic efficacy,in which the lipid-regulating,anti-oxidative and anti-inflammato-ry mechanism might be involved.
ABSTRACT
Objective To investigate the effect and molecular mechanisms of phosphatidylinositol-3 kinase(PI3K)inhibitor ZSTK474 on human melanoma A375 cells in vitro. Methods The effect of ZSTK474 on the proliferation of A375 cells was deter?mined by MTT assay.Flow cytometric analysis was carried out to examine effect of ZSTK474 on the cell cycle of A375 cells.Western-blot was conducted to evaluate the effect of ZSTK474 on the expression of the cell cycle related proteins,cyclin B1 and cdc2.Chou-Talalay method was used to evaluate the combination of ZSTK474 with PD0332991.Results In the MTT assay,ZSTK474 inhibited the proliferation of A375 cells in a dose-dependent manner with the IC50value of 1.535 μmol/L.Furthermore,ZSTK474 arrested the cell cycle progression of the A375 cells at the G2/M phase via downregulating the expression of cyclin B1 and cdc2 at 1 and 5 μmol/L. In the synergistic assay,the combination of ZSTK474 with PD0332991 in the ratio 8×IC50 ZSTK474:1×IC50 PD0332991showed a synergistic ef?fect,with the combination index(CI)values of 0.463 ± 0.113,0.658 ± 0.009 and 0.941 ± 0.034 for ED50、ED75and ED90,respectively. Conclusion ZSTK474 could inhibit the proliferation of A375 cells and arrest the cell cycle at the G2/M phase.The combination of ZSTK474 with PD0332991 could exert a synergistic effect.The precent result has revealed that the PI3K inhibitor ZSTK474 is likely to be applied alone or in combination with the CDK4/6 inhibitor PD0332991 for the human melanoma therapy.