Aim:Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-associated death.The Sonic Hedgehog(SHH)signaling pathway participates in the initiation,progression,migration,and recurrence of HCC cancer stem ...Aim:Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-associated death.The Sonic Hedgehog(SHH)signaling pathway participates in the initiation,progression,migration,and recurrence of HCC cancer stem cells.Furthermore,SHH regulates various cellular behaviors such as proliferation,differentiation,survival,self-renewal,epithelial-mesenchymal transition(EMT),and SHH autoregulation.Glioma-associated oncogene(GLI)family zinc finger are key transcription factors in the development of many organs and are deregulated in cancer.In this study,Huh-7 cells were treated with GLI-specific decoy oligodeoxynucleotide(ODN)to evaluate its anticancer impact.Methods:The transfection efficiency of GLI-specific decoy ODN was measured using fluorescent microscopy.Then,the effects of GLI-specific decoy ODN on apoptosis,viability,proliferation rate,colony formation,and migration capacities of Huh-7 cells were assessed.Furthermore,the expression of genes associated with the alteration of SHH was assessed.Results:Treatment of Huh-7 cells with GLI-specific decoy ODN decreased cell viability(56.36%±3%).Expression of certain genes such as c-MYC,SNAI2,ZEB1,and PROM1 decreased dramatically,while the expression of CDH1 increased significantly.Furthermore,the treated cells’proliferation,colony formation,and migration capacity decreased considerably.This treatment induced apoptosis in the Huh-7 cells.Conclusion:Inhibition of the SHH signaling pathway using GLI-specific decoy ODN led to a decline in the growth rate of HCC cells,decreased migration,and attenuated EMT progression.展开更多
基金supported by grants from the Royan Institute(97000205)Bahar Tashkhis Teb Co.(BTT,9703,9809,and 9903).
文摘Aim:Hepatocellular carcinoma(HCC)is one of the leading causes of cancer-associated death.The Sonic Hedgehog(SHH)signaling pathway participates in the initiation,progression,migration,and recurrence of HCC cancer stem cells.Furthermore,SHH regulates various cellular behaviors such as proliferation,differentiation,survival,self-renewal,epithelial-mesenchymal transition(EMT),and SHH autoregulation.Glioma-associated oncogene(GLI)family zinc finger are key transcription factors in the development of many organs and are deregulated in cancer.In this study,Huh-7 cells were treated with GLI-specific decoy oligodeoxynucleotide(ODN)to evaluate its anticancer impact.Methods:The transfection efficiency of GLI-specific decoy ODN was measured using fluorescent microscopy.Then,the effects of GLI-specific decoy ODN on apoptosis,viability,proliferation rate,colony formation,and migration capacities of Huh-7 cells were assessed.Furthermore,the expression of genes associated with the alteration of SHH was assessed.Results:Treatment of Huh-7 cells with GLI-specific decoy ODN decreased cell viability(56.36%±3%).Expression of certain genes such as c-MYC,SNAI2,ZEB1,and PROM1 decreased dramatically,while the expression of CDH1 increased significantly.Furthermore,the treated cells’proliferation,colony formation,and migration capacity decreased considerably.This treatment induced apoptosis in the Huh-7 cells.Conclusion:Inhibition of the SHH signaling pathway using GLI-specific decoy ODN led to a decline in the growth rate of HCC cells,decreased migration,and attenuated EMT progression.