Enhanced antitumor effect of cisplatin in human oral squamous cell carcinoma cells by tumor suppressor GRIM‑19
Authors: Zhihong Li
Fei Sun
Xin Ji
Chengmin Han
Chengxue Jin
Jia Li
Liou Jin
Minghe Li
Journal: Molecular Medicine Reports (2015)
Discipline: CLINICAL MEDICINE
Keywords: GRIM-19; tumor suppressor gene; cationic liposome; gene therapy; cisplatin
Affiliations: Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130022, P.R. China., Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China., Department of Oral and Maxillofacial Surgery, School of Stomatology Hospital of Jilin University, Changchun, Jilin 130000, P.R. China.

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&lt;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. 

Retracted: No

PubPeer comments:
 Fig 4.  Combined effect of exogenous expression of GRIM-19 and treatment with CDDP on proteins associated with apoptosis and invasion. Protein expression levels of p-p53, Stat3, Bcl-2, cyclin D1, MMP-2, MMP-9 and VEGF were analyzed using western blot assay with specific antibodies following treatment with low-dose CDDP and LP-pGRIM-19, alone and in combination. u03b2-actin was used as an internal control . ![file] The first two lanes of the Bcl-2 band are surprisingly similar to those of a frequently-used loading control, e.g. Fig 5B from [Li et al (2016)] *[left]*. Green and violet rectangles: compare with Fig 5D from Li et al *[right]*. ![file] Lanes in the MMP-9 band, marked with red and bright pink rectangles: compare with Fig 5C of [Song et al (2015)] , and other occurrences listed in that thread. ![file] I have not pursued other possible contributions to this collage. UPDATE: Another appearance of the red-boxed band here: Fig 5D from [Wang et al (2016)](http: www.ijcem.com files ijcem0017368.pdf),  IRS2 protein expression was determined in four ovarian cancer cell lines (SKOV3, A2780, OVCAR and HO-8910) and human ovarian surface epithelial cell line (HOSEpiC) . ![] The journal in that case, IJCEM, is not Pubmed accredited, and did not bother with DOIs, so it isn t possible to start a separate PubPeer thread for it. , 
 Fig 4 again. ![] The loading control also appears (identified as GAPDH) in Fig 3B of [Sang et al (2016)](http: www.ijcem.com files ijcem0019312.pdf).  PIK3R3 on ... protein level were determined in 786-O cells transfected with si-PIK3R3 or si-NC by... western blot. ![file] An IJCEM paper again. UPDATE: Another sighting! Fig 3E of [Yang et al (2015)] . ![] , 
 Fig 5A.  Representative images of the tumors in the different treatment group . ![file] Fig 6B of [Rao et al (2017)] : ![file] Fig 6 from [Zhang et al (2016)] .  **miR-22** suppresses tumor growth in a **768-O** xenograft model. (A) Photographs of tumor tissue collected after sacrifice at day 30 . ![file] Fig 4A from [Ge et al (2016)] .  **miR-497** inhibits tumor growth in vivo. (A) Representative image of tumors formed in BALB c xenograft mouse models at 28 days following injection with human osteosarcoma **MG63** cells transfected with a miR-497 mimic or miR-control. ![file] ,