Combined cetuximab and celecoxib treatment exhibits a synergistic anticancer effect on human oral squamous cell carcinoma invitro and invivo.

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) invitro and invivo. The OSCC cell line, HSC3, was treated with CET(0-400µg/ml), CXB(0-40µM), or a combination of both at a range of concentrations. Cell proliferation, apoptosis, migration and invasion were determined to assess the anticancer effects invitro. The invivo 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 invitro, and inhibited tumor growth invivo 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<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.