Enhanced antitumor effect of cisplatin in human oral squamous cell carcinoma cells by tumor suppressor GRIM‑19.

Abstract

Gene associated with retinoid‑interferon‑induced mortality19 (GRIM‑19) is a novel candidate tumor suppressor gene located on the human chromosome 19p13.1 region. Our previous study demonstrated that the upregulation of GRIM‑19 in human oral squamous cell carcinoma (OSCC) cells significantly inhibited tumor cell growth invitro and invivo. In the present study, the combined effects of cationic liposome (LP)‑mediated GRIM‑19 gene (LP‑pGRIM‑19) and the low‑dose chemotherapeutic drug, cisplatin (CDDP), on tumor cell growth invitro and invivo were examined, and the molecular mechanism of their mutual action was investigated by cell proliferation, colony formation, apoptosis, migration, invasion and western blotting assays invitro, and a node nude tumor model. It was demonstrated that cationic LP‑pGRIM‑19 gene therapy sensitized the response of breast cancer cells to CDDP, and that LP‑pGRIM‑19 in combination with CDDP significantly induced apoptosis and inhibited proliferation, colony formation, migration and invasion of the cells, compared with CDDP treatment alone. In addition, systemic treatment with a combination of intravenous injection of LP‑pGRIM‑19 and intraperitoneal injection of low‑dose CDDP into subcutaneous HSC3 human OSCC xenograft mice resulted in a significant inhibition of tumor growth (P<0.05). Further investigations indicated that the enhancement of CPPP‑mediated antitumor effects by GRIM‑19 may be associated with the upregulation of phosphorylated p53 and the downregulation of Bcell lymphoma‑2, cyclinD1, vascular endothelial growth factor, matrix metalloproteinase (MMP)‑2 and MMP‑9, the proteins of which are involved in the activation of signal transducer and activator of transcription3. The results of the present study suggested that the combination of GRIM‑19 gene therapy with low‑dose CPPP‑based chemotherapy may be a potent therapeutic strategy for the treatment of OSCC.