The Proliferation and Apoptosis Effects and Mechanisms Induced by Ursolic Acid in Human Cervical Carcinoma SiHa Cells

Objective To investigate the inhibitory and apoptosis effects and possible mechanisms of ursolic acid(UA) on the proliferation of human cervical carcinoma SiHa cells.Methods The effect of UA on the proliferation of SiHa cells was measured by MTT method.Cell cycle and apoptosis rates were observed by flow cytometry,Hoechst 33258 fluorescent dying and electron microscope were used to observe UA induced morphological changes.The gene expression of TGF-β1,Smad 4 involved in the effects of UA on SiHa cells were studied by RT-PCR.Results UA strongly inhibited the growth of SiHa cells in a dose-and time-dependent manner.Cell cycle analysis revealed that SiHa cells treated by UA for 24h,48h and 72h were blocked predominantly in G0/G1 phase(P0.05),apoptotic peak was found with flow cytometry,and the apoptosis rates were 1.16%,16.37%,and 18.70% respectively.The morphological changes of apoptosis,such as cytoplasm and nuclear condensation were observed by Hoechst 33258 fluorescent dying and electron microscope in UA treated cells.RT-PCR analysis revealed that the expression of TGF-β1mRNA decreased in a time-dependent manner and Smad 4 mRNA increased in a time-dependent manner in UA-treated cells.Conclusion UA has the effects of inhibition to SiHa cells proliferation and induction of cell apoptosis.The mechanisms may be related to the TGF-β/Smads signaling pathway.UA can up-regulated activity Smad 4 mRNA and recoved the TGF-β/Smads signaling pathway,which is related to an increased cell apoptosis.