Sato Takumi, Kakei Yasumasa, Hasegawa Takumi, Kashin Masahiko, Teraoka Shun, Yamaguchi Akinobu, Sasaki Ryohei, Akashi Masaya
Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Laboratory of Advanced Science and Technology for Industry, University of Hyogo, Kamigori 678-1205, Japan.
Cancers (Basel). 2023 Dec 3;15(23):5697. doi: 10.3390/cancers15235697.
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.
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.
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.
头颈部鳞状细胞癌(HNSCC)的治疗包括手术、放疗和免疫疗法,目的是在不影响正常组织的情况下根除癌细胞。HNSCC表达表皮生长因子受体(EGFR),西妥昔单抗是一种靶向表皮生长因子受体的IgG1单克隆抗体,已被批准用于治疗HNSCC。然而,西妥昔单抗反应性低且会引发严重副作用。据报道,金纳米颗粒(AuNPs)可增强放疗的局部抗肿瘤作用,同时不会损害正常细胞。
本研究调查了AuNPs(1.0 nM)、西妥昔单抗(30 nM)和放疗(4 Gy)单药及联合治疗对人HNSCC细胞系HSC-3的体外作用。与单药和联合治疗相比,AuNPs+西妥昔单抗+放疗联合治疗显著减少了HSC-3细胞数量和增殖,并增强了细胞凋亡。此外,将HSC-3细胞移植到裸鼠(BALB/cAJcl-nu/nu)体内的异种移植模型的体内联合治疗(AuNPs+西妥昔单抗+放疗)与对照组相比减小了肿瘤体积。扫描电子显微镜显示肿瘤组织中存在AuNPs,毒性分析表明AuNPs对正常组织没有毒性作用。
本研究表明,单独的AuNPs没有肿瘤抑制作用,但它们可使肿瘤对放疗敏感,并与西妥昔单抗结合,从而增强抗肿瘤作用。