文章：

顺铂与CXCR4拮抗剂联合疗法在口腔癌中的疗效评估

Efficacy of Cisplatin–CXCR4 Antagonist Combination Therapy in Oral Cancer

原文发布日期：25 June 2024

DOI: 10.3390/cancers16132326

类型: Article

开放获取: 是

英文摘要：

Cisplatin is a platinum-based compound that is widely used for treating inoperable oral squamous cell carcinoma (OSCC) in Japan; however, resistance to cisplatin presents a challenge and innovative approaches are required. We aimed to investigate the therapeutic potential of targeting the chemokine receptor CXCR4, which is involved in angiogenesis and tumor progression, using the CXCR4 inhibitor AMD3100, in combination with cisplatin. AMD3100 induced necrosis and bleeding in OSCC xenografts by inhibiting angiogenesis. We investigated the combined ability of AMD3100 plus cisplatin to enhance the antitumor effect in cisplatin-resistant OSCC. An MTS assay identified HSC-2 cells as cisplatin-resistant cells in vitro. Mice treated with the cisplatin-AMD combination exhibited the most significant reduction in tumor volume, accompanied by extensive hemorrhage and necrosis. Histological examination indicated thin and short tumor vessels in the AMD and cisplatin–AMD groups. These results indicated that cisplatin and AMD3100 had synergistic antitumor effects, highlighting their potential for vascular therapy of refractory OSCC. Antitumor vascular therapy using cisplatin combined with a CXCR4 inhibitor provides a novel strategy for addressing cisplatin-resistant OSCC.

摘要翻译： 

顺铂是一种铂类化合物，在日本广泛用于治疗不可手术的口腔鳞状细胞癌（OSCC），但其耐药性构成临床挑战，亟需创新治疗方案。本研究旨在探讨靶向趋化因子受体CXCR4（该受体参与血管生成与肿瘤进展）的治疗潜力，采用CXCR4抑制剂AMD3100联合顺铂进行干预。AMD3100通过抑制血管生成，诱导OSCC移植瘤发生坏死与出血。我们进一步探究了AMD3100联合顺铂对顺铂耐药OSCC的协同抗肿瘤效应。MTS实验证实HSC-2细胞在体外具有顺铂耐药特性。体内实验显示，顺铂-AMD联合治疗组小鼠肿瘤体积缩小最为显著，并伴有广泛出血及坏死。组织学检查表明AMD单药组及联合治疗组的肿瘤血管呈现细短形态。这些结果表明顺铂与AMD3100具有协同抗肿瘤作用，为难治性OSCC的血管靶向治疗提供了新思路。采用顺铂联合CXCR4抑制剂的抗肿瘤血管治疗策略，为应对顺铂耐药性OSCC开辟了新的治疗途径。

原文链接：

Efficacy of Cisplatin–CXCR4 Antagonist Combination Therapy in Oral Cancer