Mechanism Of Hedgehog Signaling Pathway In Proliferation Of Malignant Pleural Mesothelioma Cells

Objective To study the effect of inhibition of hedgehog signaling pathway on the proliferation of malignant pleural mesothelioma cells in vitro.Methods Vimodegib,a specific inhibitor of hedgehog pathway in different concentrations,was used to act on malignant pleural mesothelioma cells;CCK-8 method was used to detect cell proliferation inhibition;RT-PCR method was used to detect Gli1,VEGF,Wnt,TGF-β m RNA expression changes in malignant pleural mesothelioma cells.Results After 48 hours of treatment with vimodegib at a concentration of 25 μmol/L,the cell morphology changed;CCK-8 detection showed that after48 hours of treatment with 5,10,15,20,25 and 30 μmol/L vismodgib,the cell proliferation inhibition rates were respectively 10.31%,25.59%,34.53%,43.13%,60.69%,88.24% and vismodgib can significantly inhibit the proliferation of malignant pleural mesothelioma cells.Through further analysis,after the treatment of malignant pleural mesothelioma cells with20.38 μmol/L Vismodgib for 6,12,24,48 hours and 5,10,15,20,25 μmol/L vismodgib for48 hours,the expression of Gli1,VEGF,Wnt and TGF-β m RNA were all down regulated(P< 0.05).Conclusion The activation of hedgehog signaling pathway may be required to maintain the growth of malignant pleural mesothelioma cells.Vismodgib can significantly inhibit the proliferation of malignant pleural mesothelioma cells and down regulate the expression of target genes downstream of hedgehog signaling pathway.To clarify the function of hedgehog signal in malignant pleural mesothelioma provides a new target and approach for the treatment of malignant pleural mesothelioma.