title: Enhanced antitumor effect of cisplatin in human oral squamous cell carcinoma cells by tumor suppressor GRIM‑19.
abstract: Gene associated with retinoid‑interferon‑induced mortality 19 (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 in vitro and in vivo. 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 in vitro and in vivo were examined, and the molecular mechanism of their mutual action was investigated by cell proliferation, colony formation, apoptosis, migration, invasion and western blotting assays in vitro, 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 B cell lymphoma‑2, cyclin D1, 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 transcription 3. 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.
authors.affiliation: Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130022, P.R. China.
authors.forename: Minghe
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology Hospital of Jilin University, Changchun, Jilin 130000, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology Hospital of Jilin University, Changchun, Jilin 130000, P.R. China.
authors.forename: Liou
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology Hospital of Jilin University, Changchun, Jilin 130000, P.R. China.
authors.forename: Chengxue
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology Hospital of Jilin University, Changchun, Jilin 130000, P.R. China.
authors.forename: Chengmin
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Stomatology Hospital of Jilin University, Changchun, Jilin 130000, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130022, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009062:Mouth Neoplasms / Q000188:drug therapy*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D009361:Neoplasm Invasiveness / Q000235:genetics; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human; D002945:Cisplatin