碳离子放射治疗（CIRT）增强了恶性黑色素瘤患者的局部控制。在多个体外研究中，碳离子（C离子）也被证明可以降低黑色素瘤细胞的转移潜能。在重离子辐照后，已经显示出CXC基序10（CXCL10）在调节肿瘤转移中扮演了关键角色，并且在人类胚胎肾细胞中显著增加。本研究旨在探索C离子对黑色素瘤转移的调控作用，重点关注CXCL10在这一过程中的作用。为了探索C离子在体内对肿瘤转移的潜在调控作用，我们通过在足底注射B16F10细胞来建立肺转移小鼠模型，并对所有小鼠进行X射线和C离子治疗。随后，进行了一系列的实验，包括组织病理学分析、酶联免疫吸附测定、实时聚合酶链反应和西方印迹等，以评估C离子对黑色素瘤的调控作用。我们的结果表明，接受C离子治疗的小鼠的肿瘤血管密度显著降低，肿瘤坏死增强，肺转移缓解，并且存活期较X射线照射的小鼠更长。此外，B16F10细胞中的VEGF表达在C离子治疗组中显著降低，而在体外CXCL10沉默后可以减轻这种效应。进一步的研究发现，与HUVECs共培养可显著抑制C离子治疗组的增殖、迁移和管腔形成能力，而在C离子治疗和si-CXCL10组中观察到相反的效应。总之，我们的研究结果表明，碳离子辐射治疗可以通过特异性靶向CXCL10来抑制黑色素瘤的血管生成和肺转移。这些结果揭示了碳离子在治疗黑色素瘤中的潜在应用价值。© 2023年由放射研究学会出版。

Carbon-ion radiotherapy (CIRT) enhanced local control in patients with malignant melanoma. In several in vitro studies, carbon ions (C ions) have been also shown to decrease the metastatic potential of melanoma cells. CXC motif 10 (CXCL10) has been shown to play a crucial role in regulating tumor metastasis and it significantly increase in human embryonic kidney cells after heavy ion irradiations. This study sought to explore the regulatory effect of C ions on melanoma metastasis, emphasizing the role of CXCL10 in this process. To explore the potential regulatory effect of C ions on tumor metastasis in vivo, we developed a lung metastasis mouse model by injecting B16F10 cells into the footpad and subjected all mice to treatment with X rays and C ions. Subsequently, a series of assays, including histopathological analysis, enzyme-linked immunosorbent assay, real-time PCR, and western blotting, were conducted to assess the regulatory effects of C ions on melanoma. Our results showed that mice treated with C ions exhibited significantly less tumor vascularity, enhanced tumor necrosis, alleviated lung metastasis, and experienced longer survival than X-ray irradiated mice. Moreover, VEGF expression in B16F10 cells was significantly reduced by C-ion treatment, which could be alleviated by CXCL10 knockdown in vitro. Further investigations revealed that co-culturing with HUVECs resulted in a significant inhibition of proliferation, migration, and tube formation ability in the C-ion treated group, while the opposite effect was observed in the C-ion treated with si-CXCL10 group. In conclusion, our findings demonstrate that treatment with carbon-ion radiation can suppress angiogenesis and lung metastases in melanoma by specifically targeting CXCL10. These results suggest the potential utility of carbon ions in treating melanoma.© 2023 by Radiation Research Society.