Carbon Ion Irradiation Suppresses Tumor Growth, Migration and Invasion in X-ray Resistant Melanoma in Vitro and in Vivo.

OBJECTIVES: To investigate whether carbon ion irradiation (CIR) can overcome the inherent radioresistance of melanoma and suppress metastasis, we evaluated its effects on B16F10 cells in vitro and in vivo. 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.