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Abstract：
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：
顺铂是一种基于铂的化合物，在日本广泛用于治疗无法手术的口腔鳞状细胞癌（OSCC）；然而，对顺铂的耐药性提出了挑战，需要创新的方法。我们旨在研究靶向趋化因子受体CXCR4的治疗潜力，CXCR4与血管生成和肿瘤进展有关。使用CXCR4抑制剂AMD3100，联合顺铂。AMD3100通过抑制血管生成诱导OSCC异种移植物坏死和出血。我们研究了AMD3100加顺铂在顺铂耐药OSCC中增强抗肿瘤作用的联合能力。MTS测定在体外鉴定HSC-2细胞为顺铂抗性细胞。用顺铂-AMD组合治疗的小鼠表现出最显著的肿瘤体积减少，伴有大量出血和坏死。组织学检查表明AMD和顺铂-AMD组的肿瘤血管薄而短。这些结果表明，顺铂和AMD3100具有协同抗肿瘤作用，强调他们的血管治疗难治性OSCC的潜力。使用顺铂联合CXCR4抑制剂的抗肿瘤血管治疗为解决顺铂耐药的OSCC提供了新的策略。
