The effect of flattened and unflattened beams on apoptotic, tumor suppressor, and cell proliferation gene expression levels in preclinical malignant melanoma radiotherapy

Background/aim: The current evidence base remains lacking regarding the differences in radiobiological outcomes dependent on the presence of a flattening filter in malignant melanoma cancer (MMe Ca) radiotherapy. We designed the present study to elaborate on the malignancy-related gene expression profiles in MMe Ca tumors in response to flattening filter (FF) and flattening filter-free (FFF) beams. Materials and methods: Twenty-eight NOD-Prkdc IL2rg tm1 (NSG) mice were randomly assigned to four experimental groups. The non-engrafted Control and MMe Ca groups did not receive irradiation, while the FF-400 and FFF-1400 groups received single-dose 20 Gy radiotherapy in FF (400 MU/min) and FFF modes (1400 MU/min). B-cell lymphoma 2 (BCL-2), Bcl-2-associated x protein (BAX), phosphatase and tensin homolog (PTEN), marker of proliferation Ki-67 (Ki-67), and tumor necrosis factor alpha (TNF-α) gene expression levels were evaluated 48 hours post-radiotherapy. Results: All tested genes were significantly upregulated in the MMe Ca group compared with the Control group (p .001). Expressions of BAX, PTEN, and TNF-α were significantly higher (p .001) in the MMe Ca plus radiotherapy groups, depending on the different dose rates. Significant differences in BAX and PTEN levels were found in response to FF and FFF beams (p .001). Ki-67 and BCL-2 were decreased after radiotherapy (p .001), with the FFF beam exerting a more prominent effect than the FF beam (p .001). Conclusion: Our results indicate that both FF and FFF beams effectively induce radiobiological changes regarding apoptosis, tumor suppression, and cell proliferation processes, while the FFF beam is superior to the FF beam in MMe Ca.