Combined cetuximab and celecoxib treatment exhibits a synergistic anticancer effect on human oral squamous cell carcinoma in vitro and in vivo
Authors: Donghua Qian
Yanmin Zhou
Yang Li
Hongyu Jing
Chengyuan Ma
Ming Qian
Journal: Oncology Reports (2014)
Discipline: CLINICAL MEDICINE
Keywords: epidermal growth factor receptor (EGFR); cetuximab (CET); celecoxib (CXB); oral squamous cell carcinoma (OSCC); in vitro
Affiliations: Prosthodontics Department of the Stomatological Hospital, Jilin University, Changchun, Jilin 130021, P.R. China., Department of Respiration, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China., Department of Neurosurgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China., Implantology Department of the Stomatological Hospital, Jilin University, Changchun, Jilin 130021, P.R. China.

Abstract:  The aim of the present study was to evaluate the potency of epidermal growth factor receptor (EGFR) pathway inhibition achieved by combining cetuximab (CET), an anti-EGFR monoclonal antibody, and celecoxib (CXB), a cyclooxygenase-2 (COX-2) inhibitor, in oral squamous cell carcinoma (OSCC) in vitro and in vivo. The OSCC cell line, HSC3, was treated with CET (0-400 µg/ml), CXB (0-40 µM), or a combination of both at a range of concentrations. Cell proliferation, apoptosis, migration and invasion were determined to assess the anticancer effects in vitro. The in vivo effects of CET and CXB on tumor cell growth were examined using an OSCC xenograft nude mouse model. In addition, downstream protein expression levels of EGFR, p-EGFR, PI3K, p-PI3K, AKT and p-Akt were evaluated by western blot analysis. It was found that the combination of low concentrations of CET and CXB significantly suppressed the proliferation, migration and invasion of the HSC3 tumor cells and decreased PEG2 production and VEGF expression in vitro, and inhibited tumor growth in vivo compared to the action of either agent alone. The results also showed that this combination significantly induced apoptosis and increased caspase-3 and caspase-8 activity compared to the action of either agent alone (P&lt;0.01). Furthermore, the combination treatment significantly reduced the expression of p-EGFR, p-PI3K and p-Akt in the HSC3 cell line, which may contribute to the inhibition of tumor growth. Taken together, our findings revealed that the additive combination of CET and CXB is a potential drug candidate for the treatment of OSCC. 

Retracted: No

PubPeer comments:
 Western blot band duplications and figure duplications with PLOS One 10.1371 journal.pone.0054841: 1) Figure 3A and 6A use the same GAPDH bands: ![file] 2) Figure 2A B is identical with Figure 2 in PLOS One 10.1371 journal.pone.0054841 **CNS Neurosci Ther** ![file] **PLOS ONE** ![file] 3) Figure 5A spinal cords iNOS and GAPDH bands with Figure 6a in PLOS One 10.1371 journal.pone.0054841: **CNS Neurosci Ther** ![file] **PLOS ONE** ![file] , 
 In addition to the issues identified before, the authors also reused part of Figure 2 from the CNS Neurosci Ther and PLOS ONE papers in this manuscript in Figure 2d: J Mol Neurosci. 2015 Mar;55(3):725-32. doi: 10.1007 s12031-014-0411-7. Epub 2014 Sep 16. The therapeutic potential of Rho kinase inhibitor fasudil derivative FaD-1 in experimental autoimmune encephalomyelitis. Zhao YF1, Zhang X, Ding ZB, Yang XW, Zhang H, Yu JZ, Li YH, Liu CY, Zhang Q, Zhang HZ, Ma CG, Xiao BG. ![file] ,