Introduction: Head and neck squamous cell carcinoma (HNSCC) treatment includes surgery, radiotherapy, and immunotherapy with the aim of eradicating cancer cells without affecting normal tissues. HNSCC expresses epidermal growth factor receptor (EGFR) and cetuximab, an IgG1 monoclonal antibody targeting epidermal growth factor receptor, has been approved for the treatment of HNSCC. However, cetuximab has low reactivity and induces serious side effects. Gold nanoparticles (AuNPs) were reported to enhance the local antitumor effects of radiotherapy without damaging normal cells. Methods and Results: This study investigated the in vitro effects of single and combination therapy with AuNPs (1.0 nM), cetuximab (30 nM), and radiotherapy (4 Gy) on a human HNSCC cell line, HSC-3. Combination treatment of AuNPs + cetuximab + radiotherapy markedly reduced HSC-3 numbers and proliferation and enhanced apoptosis compared with single and double combination treatments. Furthermore, the in vivo combination treatment (AuNPs + cetuximab + radiotherapy) of a xenograft model of HSC-3 cells transplanted into nude mice (BALB/cAJcl-nu/nu) reduced the tumor volume compared with the controls. Scanning electron microscopy demonstrated the presence of AuNPs in tumor tissues and toxicity analysis indicated that AuNPs had no toxic effect on normal tissues. Conclusions: This study showed that AuNPs alone do not have a tumor-suppressing effect, but they sensitize tumors to radiotherapy and bind to cetuximab, leading to enhanced antitumor effects.
引言:头颈部鳞状细胞癌的治疗手段包括手术、放疗及免疫疗法,旨在清除癌细胞的同时保护正常组织。该肿瘤表达表皮生长因子受体,靶向该受体的IgG1单克隆抗体西妥昔单抗已被批准用于临床治疗。然而,西妥昔单抗存在反应率低且易引发严重副作用的问题。研究表明,金纳米颗粒能增强放疗的局部抗肿瘤效果,且对正常细胞无损伤。 方法与结果:本研究通过体外实验探讨了金纳米颗粒、西妥昔单抗及放射治疗对头颈部鳞癌HSC-3细胞系的单独及联合作用效应。实验结果显示,与单一或双联疗法相比,金纳米颗粒联合西妥昔单抗及放疗的三联疗法能显著抑制HSC-3细胞增殖、促进细胞凋亡。在裸鼠移植瘤模型中,三联疗法较对照组显著缩小了肿瘤体积。扫描电镜证实肿瘤组织中存在金纳米颗粒,毒性分析表明其对正常组织无毒性作用。 结论:本研究表明金纳米颗粒本身无直接抑瘤作用,但能增强肿瘤对放疗的敏感性,并与西妥昔单抗产生协同效应,从而显著提升抗肿瘤疗效。