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Biosci 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.

Author information

1
Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College.
2
Department of Gynaecology and Obstetrics, Second Hospital of Jilin University.
3
Department of Gastroenterology, First Hospital of Jilin University.
4
Department of Pathophysiology, Basic Medicine School of Jilin University.
5
Department of Recovery, Nursing School of Jilin University.

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.

KEYWORDS:

GRIM-19; Stat3; apoptosis; hepatocellular carcinoma; orthotopically implanted tumor

PMID:
31527330
DOI:
10.5582/bst.2019.01185
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