Bhuvaneswari Ramaswamy, Ng Qin Feng, Thong Patricia S P, Soo Khee-Chee
National Cancer Centre Singapore, Division of Medical Sciences, Singapore 169610, Singapore.
Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
Oncotarget. 2015 May 30;6(15):13487-505. doi: 10.18632/oncotarget.3622.
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.
口腔鳞状细胞癌（OSCC）占所有口腔癌的90%，其特点是预后差、生存率低。表皮生长因子受体（EGFR）在口腔癌中高表达，是癌症治疗和预防的靶点。在本研究中，我们评估了光动力疗法（PDT）联合EGFR抑制剂尼妥珠单抗在口腔癌细胞系和OSCC异种移植肿瘤模型中的疗效。PDT是一种有前景的微创治疗方式，它涉及光敏剂、分子氧和光的相互作用以破坏肿瘤。我们证明，EGFR抑制剂尼妥珠单抗和西妥昔单抗通过抑制口腔癌细胞系和人内皮细胞的迁移和侵袭而具有抗血管生成特性。EGFR抑制剂还显著减少了内皮细胞的管腔形成。叶绿素e6-PDT联合尼妥珠单抗和西妥昔单抗可降低不同口腔癌细胞和内皮细胞的增殖。此外，我们的体内研究表明，与对照和PDT治疗的肿瘤相比，PDT与尼妥珠单抗的联合治疗可协同延缓肿瘤生长。联合治疗的肿瘤中观察到EGFR、Ki-67和CD31的下调。肝肾功能标志物分析显示无治疗相关毒性。总之，口腔癌与EGFR抑制剂尼妥珠单抗联合使用时，光动力疗法的疗效可以提高。
