Effect of matrine on the chemosensitivity of cisplatin in lung cancer A549 cells through Hedgehog signaling pathway
Objective To investigate the effect of matrine on the chemotherapy sensitivity to cisplatin(DDP)in lung cancer A549 cells through Hedgehog signaling pathway.Methods Thiazolyl blue(MTT)method was used to detect the effect of matrine at different concentrations on the proliferation of A549 cells,and the 20%lethal concentration(LC20)was calculated.A549 cells grown in log phase were divided into control group,matrine group(treated with LC20 matrine),Hedgehog signaling pathway inhibitor group(HPI-4)group(treated with 5 μmol·L-1 HPI-4),DDP group(treated with 5 mg·L-1 DDP),DDP+matrine group(treated with 5 mg·L-1 DDP and LC20 matrine)and DDP+matrine+HPI-4 group(treated with 5 mg·L-1 DDP,LC20 matrine and 5 μmol·L-1 HPI-4),each group had 3 replicate holes.MTT method and flow cytometry were used to detect the survival rate and apoptosis rate of cells in each group after 48 hours of intervention.Western blotting was used to detect the expression of Hedgehog signaling pathway related proteins sonic hedgehog(SHH),patched1(Ptch1)and glioma-associated oncogene homolog 1(Glis1)in each group.Results Compared with the control group,the cell survival rate of the intervention group with different concentrations of matrine was reduced(P<0.05),and the cell survival rate decreased with the increase of matrine dose(P<0.05).Compared with the control group,the cell survival rate of the matrine group,HPI-4 group,DDP group,DDP+matrine group and DDP+matrine+HPI-4 group decreased,and the DDP+matrine+HPI-4 group<DDP+Matrine group<DDP group<matrine group and HPI-4 group(P<0.05).The result of apoptosis rate was opposite to the above.Compared with the control group,the relative expressions of Hedgehog signaling pathway SHH,Ptch1,Glis1 proteins in the matrine group,HPI-4 group,DDP group,DDP+matrine group,and DDP+matrine+HPI-4 group were all decreased,and DDP+matrine+HPI-4 group<HPI-4 group<DDP+matrine group<DDP group and matrine group(P<0.05).Conclusion Matrine can increase the sensitivity of lung cancer A549 cells to DDP chemotherapy,and its mechanism of action may be related to the inhibition of Hedgehog signaling pathway.
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