Effect Of Hedgehog Inhibitor Vismodegib On Proliferation Of Kras Gene Mutation Lung Cancer Cells

Background: With tremendous advancement of the targeted therapy of lung cancer in recent years,a variety of molecular driver genes have been discovered successively,and novel target drugs have been introduced one by one.However,since targeted therapy drugs based on driver gene KRAS have not been approved,no significant progress in the treatment of lung cancer patients with KRAS mutation has been achieved.Hedgehog signaling pathway participates in the occurrence and development of lung cancer.Therefore,by inhibiting Hedgehog pathway activation,it is hope to provide new strategies for the treatment of lung cancer patients with KRAS mutation.Objective: to investigate the mechanism of regulating the proliferation of lung cancer cells with KRAS mutation by blocking the Hedgehog signaling pathway through in vitro cell experiments.Methods: different concentrations of Hedgehog pathway inhibitor Vismodegib are added to act on A549,a lung cancer cell with KRAS mutation,an inverted microscope is used to observe the changes in cell morphology;the proliferation inhibition status of cell is detected using CCK8 method;The m-RNA and protein expression levels of Smo,Gli1,E-Cadherin,and β-Catenin in KRAS mutant lung cancer cells are detected using RT-PCR method through Western blotting experiment.Results: After the treatment of cell in the experimental group with 10,20,30,40,50 μmol/L Vismodegib for 48 hours,the corresponding cell proliferation inhibition rates were 13.74%,22.73%,30.15%,41.90%,51.69%,respectively.Through calculation,IC50 concentration was 51.89μmol/L.After the treatment of cell by 10μmol/L,20μmol/L,30μmol/L,40μmol/L,50μmol/L concentration Vismodegib,levels of Smo,Gli1 m RNA and protein expression decreased,levels of E-Cadherin,β-Catenin m RNA and protein expression increased.Conclusion: The activation of Hedgehog signaling pathway is one of the prerequisite conditions to maintain the growth of NSCLC with KRAS mutation.Vismodegib can further down-regulate the expression of Smo and Gli1 genes in A549 cell through specific inhibition of Smo protein,thereby inhibiting the proliferation of A549 cell.It can up-regulate E-Cadherin and β-Catenin genes to enhance cell adhesion and reduce tumor cell metastasis.By blocking the Hedgehog signaling pathway to inhibit the transcription and translation of its downstream target genes,it is presumably conductive to the treatment of NSCLC patient with KRAS mutation.