Yoshida Saori, Kawai Hotaka, Soe Yamin, Eain Htoo Shwe, Sanou Sho, Takabatake Kiyofumi, Takeshita Yohei, Hisatomi Miki, Nagatsuka Hitoshi, Asaumi Junichi, Yanagi Yoshinobu
Preliminary Examination Room, Okayama University Hospital, Okayama 700-8558, Japan.
Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8525, Japan.
Cancers (Basel). 2024 Jun 25;16(13):2326. doi: 10.3390/cancers16132326.
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.
顺铂是一种铂类化合物，在日本被广泛用于治疗无法手术的口腔鳞状细胞癌（OSCC）；然而，对顺铂的耐药性带来了挑战，需要创新方法。我们旨在研究使用CXCR4抑制剂AMD3100靶向趋化因子受体CXCR4（其参与血管生成和肿瘤进展）与顺铂联合使用的治疗潜力。AMD3100通过抑制血管生成诱导OSCC异种移植瘤发生坏死和出血。我们研究了AMD3100加顺铂增强对顺铂耐药的OSCC抗肿瘤作用的联合能力。MTS分析确定HSC-2细胞在体外为顺铂耐药细胞。用顺铂-AMD组合治疗的小鼠肿瘤体积减小最为显著，伴有广泛出血和坏死。组织学检查表明，AMD组和顺铂-AMD组的肿瘤血管细且短。这些结果表明顺铂和AMD3100具有协同抗肿瘤作用，突出了它们在难治性OSCC血管治疗中的潜力。使用顺铂联合CXCR4抑制剂进行抗肿瘤血管治疗为解决顺铂耐药的OSCC提供了一种新策略。
