Qian Yichun, Qiu Mantang, Wu Qingquan, Tian Yanyan, Zhang Yu, Gu Ning, Li Suyi, Xu Lin, Yin Rong
1] Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, P.R. China 210009 [2] The First Clinical College, Nanjing Medical University, Nanjing, P.R. China 210029.
Department of Thoracic Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, P. R. China 223300.
Sci Rep. 2014 Dec 15;4:7490. doi: 10.1038/srep07490.
Cetuximab (C225) is a unique agent, targeting epidermal growth factor receptor (EGFR)-positive cancer. However, the therapeutic effect of C225 in EGFR high-expressing non-small cell lung cancer (NSCLC) remains poor. Here, we report that conjugation of C225 with gold nanoparticles (AuNPs) enhances the cytotoxicity of C225 in NSCLC both in vitro and in vivo. The NSCLC cell lines A549 (EGFR(high)) and H1299 (EGFR(low)) were employed to investigate different responses to C225, IgG-AuNPs and C225-AuNPs. The antitumor properties of C225-AuNPs were explored in vivo by establishing a tumor xenograft model in nude mice. Overall, the therapeutic effect of C225-AuNPs was more pronounced in EGFR(high) A549 cells compared with EGFR(low) H1299 cells. The cytotoxic effect of C225-AuNPs in A549 cells increased in a dose-dependent manner. C225-AuNPs significantly suppressed A549 cell proliferation and migration capacity and accelerated apoptosis compared with C225, and this effect was probably due to enhanced EGFR endocytosis and the subsequent suppression of downstream signaling pathway. Finally in the tumor xenograft of nude mice, treatment with C225-AuNPs also led to a significant reduction in tumor weight and volume with low toxicity. Our findings suggest that C225-AuNPs conjugate has promising potential for targeted therapy of EGFR positive NSCLC patients.
西妥昔单抗（C225）是一种独特的药物，靶向表皮生长因子受体（EGFR）阳性癌症。然而，C225在EGFR高表达非小细胞肺癌（NSCLC）中的治疗效果仍然不佳。在此，我们报告C225与金纳米颗粒（AuNPs）偶联可增强C225在体外和体内对NSCLC的细胞毒性。采用NSCLC细胞系A549（EGFR(高)）和H1299（EGFR(低)）来研究对C225、IgG-AuNPs和C225-AuNPs的不同反应。通过在裸鼠中建立肿瘤异种移植模型来探索C225-AuNPs的抗肿瘤特性。总体而言，与EGFR(低)的H1299细胞相比，C225-AuNPs在EGFR(高)的A549细胞中的治疗效果更显著。C225-AuNPs对A549细胞的细胞毒性呈剂量依赖性增加。与C225相比，C225-AuNPs显著抑制A549细胞增殖和迁移能力并加速细胞凋亡，这种作用可能是由于增强了EGFR内吞作用以及随后对下游信号通路的抑制。最后，在裸鼠的肿瘤异种移植模型中，用C225-AuNPs治疗也导致肿瘤重量和体积显著降低且毒性较低。我们的研究结果表明，C225-AuNPs偶联物在EGFR阳性NSCLC患者的靶向治疗中具有广阔的应用前景。
