GRIM-19 over-expression represses the proliferation and invasion of orthotopically implanted hepatocarcinoma tumors associated with downregulation of Stat3 signaling.

Abstract

The retinoid-interferon-induced mortality-19 (GRIM-19) gene has been identified as a negative regulator associated with tumor development. The current study created a model of an orthotopically implanted hepatocarcinoma tumor to verify the inhibitory effect of GRIM-19 in vivo. After treatment with GRIM-19 carried by attenuated Salmonella, transplanted tumors were measured with an Imaging System. The expression of GRIM-19, Stat3/p-Stat3, cyclinD1, CDK4, PCNA, Bax/Bcl-2, cleaved caspase-9/3, VEGF, and MMP-2/9 was determined using immunohistochemistry and Western blot analysis. The cell cycle was assessed using flow cytometry (FCM). Apoptosis was determined using FCM and a TUNEL assay. Results indicated that GRIM-19 overexpression resulted in inhibition of peritoneal metastasis, induction of cell cycle arrest, and apoptosis in vivo. In addition, the expression of Stat3/p-Stat3 was down-regulated by GRIM-19. These results suggest that GRIM-19 overexpression could suppress the growth of orthotopically implanted hepatocarcinoma tumors by reversing the regulation of the Stat3 signaling pathway. This approach could potentially be a powerful treatment for hepatocarcinoma.