ABSTRACT
To explore the inhibitory effect of timosaponin AⅢ on the proliferation of human glioblastoma cell line U87MG and investigate its related mechanism. As compared with the model group, the tumor weight was significantly reduced in timosaponin AⅢ-treated group. Timosaponin AⅢinhibited the proliferation of U87MG cell line in a dose-dependent manner. It up-regulated the gene and protein expression levels of p21, meanwhile inhibited the protein expression levels of β-Catenin, Cyclin D1 and Bcl-2. It also inhibited the translocation of β-Catenin into nucleus, suppressed the phosphorylation expression of ERK, but increased the phosphorylation expression of p38 and JNK. Combined use of JNK inhibitor SP600125 and p38 inhibitor SB203580 could decrease p21 and increase β-Catenin protein expressions. Timosaponin AⅢ inhibited the proliferation of human glioblastoma cell line U87MG partly by intervening MAPK and Wnt/β-Catenin signal pathways.
ABSTRACT
Objective:To observe the effect of timosaponin AⅢon the proliferation of cultured melanoma B16 and A375 cells and nitrite produced from macrophage activation. Methods:MTT assay was adopted to detect the cell growth inhibition. The morphological changes of B16 and A375 cells were observed under an inverted microscope. Nitrite production of activated mouse macrophages induced by lipopolysaccharide ( LPS) plus IFN-γ was measured by Griess assay. Results: Timosaponin AⅢ could significantly inhibit the growth of B16 cells at the concentration of 16 μmol·L-1 after the 48- and 72-hour treatment, and significantly inhibit the growth of A375 cells at the concentration ranged from 4 to 16 μmol·L-1 after the 48-and 72-hour treatment. Shrinkage, vacuoles and necrosis of B16 and A375 cells were observed after the 48-and 72-hour treatment by 16μmol·L-1 timosaponin AⅢ,the other concentration of timosaponin AⅢ showed no notable effect on B16 cells and vacuoles of A375 cells appeared at the concentration from 4 to 16 μmol· L-1. Compared with RAW 264. 7 stimulated LPS plus IFN-γ,timosaponin AⅢ could significant inhibit nitrite production of macro-phage inflammatory cell model at the concentration of 10μmol·L-1(P<0. 01). Conclusion:Timosaponin AⅢcan inhibit the prolif-eration of melanoma B16 and A375 cells and macrophage inflammation,suggesting it has anti-tumor and anti-inflammatory effects . The anti-tumor effect of timosaponin AⅢ may be related to the inhibition of tumor inflammation.