研究概要
非小细胞肺癌(NSCLC)是肺癌的主要形式,也是全球癌症相关死亡的主要原因,这主要归因于其侵袭性进展和对当前疗法的耐药性。
中文摘要
非小细胞肺癌(NSCLC)是肺癌的主要形式,也是全球癌症相关死亡的主要原因,这在很大程度上归因于其侵袭性进展和对当前疗法的耐药性。B7-H3已成为一个值得研究的新型免疫治疗靶点。木犀草素是一种在蔬菜和草药中大量存在的黄酮类多酚化合物,已在多种癌症类型中显示出显著的抗肿瘤作用。然而,其在NSCLC中的治疗作用机制仍知之甚少。本研究旨在探讨木犀草素与B7-H3靶向免疫治疗在NSCLC中的联合效应。结果表明,木犀草素以剂量依赖性方式抑制NSCLC细胞增殖,并与B7-H3抑制表现出增强的联合效应,同时还促进细胞凋亡。该联合策略在体外和体内均产生了显著的抑制作用。构建了一种靶向B7-H3的双特异性杀伤细胞衔接器(BiKE),并测量了抗体依赖性细胞介导的细胞毒性(ADCC)以评估其与木犀草素的联合效应。与单独使用木犀草素或BiKE相比,靶向B7-H3的BiKE与木犀草素联合时表现出更优的活性。我们的发现不仅将B7-H3确定为NSCLC的一个有前景的治疗靶点,还表明木犀草素可作为一种潜在的抗癌佐剂。本文提出的合理设计的联合策略可能会增强NSCLC的现有治疗模式。
展开英文摘要原文
Non-small-cell lung cancer (NSCLC) is the predominant form of lung cancer and the leading cause of cancer-related mortality worldwide, largely due to its aggressive progression and resistance to current therapies. B7-H3 has emerged as a novel immunotherapeutic target worthy of investigation. Luteolin, a flavonoid polyphenolic compound abundantly present in vegetables and herbs, has demonstrated significant anti-tumor effects in various cancer types. However, its therapeutic mechanism of action in NSCLC remains poorly understood. This study aimed to examine the combined effects of luteolin and B7-H3-targeted immunotherapy in NSCLC. The results demonstrated that luteolin suppressed NSCLC cell proliferation in a dose-dependent manner and exhibited enhanced combined effects with B7-H3 inhibition, while also promoting apoptosis. This combination strategy produced significant inhibitory effects both in vitro and in vivo . A B7-H3-targeted bispecific killer cell engager (BiKE) was constructed, and antibody-dependent cell-mediated cytotoxicity (ADCC) was measured to evaluate its combined effect with luteolin. The B7-H3-targeted BiKE showed superior activity when combined with luteolin compared to either treatment of luteolin or BiKE alone. Our findings not only identify B7-H3 as a promising therapeutic target for NSCLC but also suggest luteolin as a potential anticancer adjuvant. The rationally designed combination strategy presented here may enhance existing treatment paradigms for NSCLC.
论文信息
- 作者
- Yang S、Zhang Z、He X、Ouyang Z、Tang S、Liang M、Chen Z、Liu Y
- 第一作者单位
- Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, China.China
- 通讯作者单位
- Cancer Centre, Institute of Translational Medicine, Department of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, China.China
- 期刊
- International journal of biological sciences2026