Synergistic inhibitory effects of cetuximab and curcumin on human cisplatin-resistant oral cancer CAR cells through intrinsic apoptotic process.

Abstract

Cetuximab, an epidermal growth factor receptor (EGFR)-targeting monoclonal antibody (mAb), is a novel targeted therapy for the treatment of patients with oral cancer. Cetuximab can be used in combination with chemotherapeutic agents to prolong the overall survival rates of patients with oral cancer. Curcumin is a traditional Chinese medicine, and it has been demonstrated to have growth-inhibiting effects on oral cancer cells. However, information regarding the combination of cetuximab and curcumin in drug-resistant oral cancer cells is lacking, and its underlying mechanism remains unclear. The purpose of the present study was to explore the oral anticancer effects of cetuximab combined with curcumin on cisplatin-resistant oral cancer CAR cell apoptosis in vitro. The results demonstrated that combination treatment synergistically potentiated the effect of cetuximab and curcumin on the suppression of cell viability and induction of apoptosis in CAR cells. Cetuximab and curcumin combination induced apoptosis and dramatically increased caspase-3 and caspase-9 activities compared with singular treatment. Combination treatment also markedly suppressed the protein expression levels of EGFR and mitogen-activated protein kinases (MAPKs) signaling (phosphorylation of ERK, JNK and p38). The results demonstrated that co-treatment with cetuximab and curcumin exerts synergistic oral anticancer effects on CAR cells through the suppression of the EGFR signaling by regulation of the MAPK pathway.