BioScience Trends. 2019;13(4):342-350. (DOI: 10.5582/bst.2019.01185)

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

Kong DX, Chen JY, Sun X, Lin Y, Du YW, Huang D, Cheng HJ, He P, Yang LL, Wu S, Zhao LJ, Meng XW


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.

KEYWORDS: GRIM-19, hepatocellular carcinoma, orthotopically implanted tumor, Stat3, apoptosis

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