Carbon Ion Irradiation Suppresses Tumor Growth, Migration and Invasion in X-ray Resistant Melanoma in Vitro and in Vivo
Sha Li, Zhenghua Ren, Hefa Huang, Huiyan Pang, Hongyu Luo, Zhengli Wei, Xiaoyang Yin, Mengjie Xing, Xiaoqin Li, Aihong MaoObjectives
To investigate whether carbon ion irradiation (CIR) can overcome the inherent radioresistance of melanoma and suppress metastasis, we evaluated its effects on B16F10 cells
Methods
B16F10 cells and C57BL/6J tumor-bearing mice were irradiated with either 4-MV X-rays or 290 MeV/nucleon carbon ions at different doses. Metastatic ability was assessed by wound-healing, Transwell migration, and Matrigel invasion assays. Expression of metastasis-related proteins, including MMP2, MMP9, N-cadherin, and E-cadherin, was analyzed by Western blotting or immunohistochemistry (IHC). Tumor growth and survival were recorded, and H&E staining was performed for histopathological evaluation.
Results
Under identical physical-dose conditions, CIR suppressed cell migration and invasion more effectively than XIR, especially at 2.5 and 7.5 Gy. These effects were accompanied by reduced expression of MMP2, MMP9, and N-cadherin, along with increased E-cadherin expression. Furthermore, 7.5 Gy CIR significantly suppressed tumor growth, reduced tumor volume, and prolonged survival in tumor-bearing mice, although tumor regrowth was observed after 21 days. Conversely, 0.5 Gy XIR exerted promoting effects, while 2.5 Gy XIR only had a slight impact.
Conclusion
These findings highlight the antimetastatic potential of CIRT against radioresistant melanoma. However, further validation with RBE-adjusted doses, human cell models, and metastasis-related endpoints is warranted.