Carbon Ions Suppress Angiogenesis and Lung Metastases in Melanoma by Targeting CXCL10

黑色素瘤 转移 癌症研究 体内 化学 体外 CXCL10型 血管生成 基因敲除 病理 医学 分子生物学 生物 细胞凋亡 内科学 癌症 炎症 生物化学 趋化因子 生物技术
作者
Chengcheng Li,Qiuning Zhang,Hui Luo,Ruifeng Liu,Shuangwu Feng,Yichao Geng,Lina Wang,Yang Zhang,Yanying Zhang,Xiaohu Wang
出处
期刊:Radiation Research [BioOne (Radiation Research Society)]
卷期号:200 (3)
标识
DOI:10.1667/rade-22-0086.1
摘要

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.
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