Nimotuzumab increases the anti-tumor effect of photodynamic therapy in an oral tumor model

Abstract

// Ramaswamy Bhuvaneswari 1 , Qin Feng Ng 1 , Patricia S.P Thong 1 , Khee-Chee Soo 1, 2 1 National Cancer Centre Singapore, Division of Medical Sciences, Singapore 169610, Singapore 2 Duke-NUS Graduate Medical School, Singapore 169857, Singapore Correspondence to: Ramaswamy Bhuvaneswari, e-mail: dmsram@nccs.com.sg Keywords: photodynamic therapy, epidermal growth factor receptor, nimotuzumab, oral squamous cell carcinoma, angiogenesis Received: October 20, 2014      Accepted: April 08, 2015      Published: April 20, 2015 ABSTRACT Oral squamous cell carcinoma (OSCC) represents 90% of all oral cancers and is characterized with poor prognosis and low survival rate. Epidermal growth factor receptor (EGFR) is highly expressed in oral cancer and is a target for cancer therapy and prevention. In this present work, we evaluate the efficacy of photodynamic therapy (PDT) in combination with an EGFR inhibitor, nimotuzumab in oral cancer cell lines and OSCC xenograft tumor model. PDT is a promising and minimally invasive treatment modality that involves the interaction of a photosensitizer, molecular oxygen and light to destroy tumors. We demonstrated that EGFR inhibitors nimotuzumab and cetuximab exhibits anti-angiogenic properties by inhibiting the migration and invasion of oral cancer cell lines and human endothelial cells. The EGFR inhibitors also significantly reduced tube formation of endothelial cells. Chlorin e6-PDT in combination with nimotuzumab and cetuximab reduced cell proliferation in different oral cancer and endothelial cells. Furthermore, our in vivo studies showed that the combination therapy of PDT and nimotuzumab synergistically delayed tumor growth when compared with control and PDT treated tumors. Downregulation of EGFR, Ki-67 and CD31 was observed in the tumors treated with combination therapy. Analysis of the liver and kidney function markers showed no treatment related toxicity. In conclusion, PDT outcome of oral cancer can be improved when combined with EGFR inhibitor nimotuzumab.