Derivate Isocorydine (d-ICD) Suppresses Migration and Invasion of Hepatocellular Carcinoma Cell by Downregulating ITGA1 Expression

Abstract

In our previous studies, we found that isocorydine (ICD) could be a potential antitumor agent in hepatocellular carcinoma (HCC). Derivate isocorydine (d-ICD), a more effective antitumor agent, has been demonstrated to inhibit proliferation and drug resistance in HCC. In order to investigate the potential role of d-ICD on HCC cell migration and its possible mechanism, wound healing assay, trans-well invasion assay, western blot analysis, and qRT-PCR were performed to study the migration and invasion ability of HCC cells as well as relevant molecular alteration following d-ICD treatment. Results indicated that the migration and invasion ability of HCC cells were suppressed when cultured with d-ICD. Meanwhile, the expression level of <i>ITGA1</i> was markedly reduced. Furthermore, we found that <i>ITGA1</i> promotes HCC cell migration and invasion in vitro, and that <i>ITGA1</i> can partly reverse the effect of d-ICD-induced migration and invasion suppression in HCC cells. In addition, dual luciferase reporter assay and chromatin immunoprecipitation assay were used to study the expression regulation of <i>ITGA1</i>, and found that <i>E2F1</i> directly upregulates <i>ITGA1</i> expression and d-ICD inhibits <i>E2F1</i> expression. Taken together, these results reveal that d-ICD inhibits HCC cell migration and invasion may partly by downregulating <i>E2F1</i>/<i>ITGA1</i> expression.