Molecular Mechanism Of Derivative Isocorydine (d-ICD) To Inhibit Cell Migration And Invasion Of Hepatocellular Carcinoma Cells

Hepatocellular carcinoma(HCC)is one of the common malignant tumors,with a feature of high morbidity and mortality.As one of the three major anti-tumor therapies,chemotherapy is the main treatment for terminal-stage HCC patients.However,chemotherapeutics for HCC are numbered,and their curative effects are not satisfied.Therefore,it is important to exploring an effective drug for HCC.Isocorydine(ICD),as an alkaloid,is purified from Papaveraceae sp.plants,such as Dactylicapnos scandens Hutchins and Dicranostigma leptopodum(Maxim.)Fedde.Our previous studies have demonstrated that ICD may be a potential anti-HCC agent.But,the effective dosage has been proposed to be too high to apply in clinical trial.Derivate isocorydine(d-ICD),with the modified chemical structure of ICD,has been proved to be more effective regarding anticancer activity.Our previous studies showed that d-ICD suppressed HCC cell proliferation both in vitro and in vivo,and d-ICD inhibited drug resistance and improved the sensitivity of HCC cell to chemotherapeutic drug at a lower dosage.However,whether d-ICD exerts an effect on migration and invasion of HCC cells remains unclear.In this study,we observed that d-ICD obviously inhibited HCC cell migration and invasion in vitro.Further exploring the relevant molecular mechanisms,we found that d-ICD obviously inhibited ITGA1 expression.ITGA1 codes integrin alpha 1,which participates in mediating adhesion of cell-to-cell and cell-to-extracellular matrix.In this study,we found that ITGA1 overexpression promoted HCC cell migration and invasion,ITGA1 down-expression inhibited HCC cell migration and invasion.Moreover,ITGA1 overexpression significantly weaken d-ICD-induced migration and invasion inhibition in HCC cells.Further studies showed that E2F1 transcriptional upregulated ITGA1 expression,and d-ICD inhibited E2F1 expression in HCC cell.In summary,these results indicated that d-ICD inhibits HCC cell migration and invasion partly by suppressing ITGA1 expression,and help to better understand the anti-tumor effects and mechanism of d-ICD.