Anti-Tumour Activity of Fotemustine and Protons in Combination with Bevacizumab

Abstract

Background: Metastatic melanoma is one of the most aggressive tumours and is also very resistant to current therapeutic approaches. The aim of this investigation was the in vitro study of the anti-proliferative effects of fotemustine (FM; 100 and 250 µM), bevacizumab (5 µg/ml) and proton irradiation (12 and 16 Gy) on resistant HTB140 human melanoma cells. Methods: Viability was estimated by sulphorhodamine B assay, while cell proliferation was analyzed by 5-bromo-2-deoxyuridine assay. Cell cycle distribution and apoptosis were examined using flow cytometry. Results: Cell viability and proliferation were reduced after all applied treatments. The level of apoptosis significantly increased after treatment with FM, protons or a combination of all agents, while the apoptotic index ranged from 1.2 to 9.2. Proton irradiation, as well as combined treatment with bevacizumab and protons or 100 µM FM, bevacizumab and protons, have reduced melanoma cell proliferation through the induction of G1 phase arrest. Single FM (250 µM) or bevacizumab treatment and their combination, as well as the joint application of these 2 agents with protons, reduced cell proliferation and provoked G2 phase accumulation. Conclusion: The analyzed treatments reduced cell viability and proliferation, triggered G1 or G2 cell cycle phase accumulation and stimulated apoptotic cell death.

A Critical Review of Radiation Therapy: From Particle Beam Therapy (Proton, Carbon, and BNCT) to Beyond

“…The number of relevant studies has increased from approximately 30 in 2010 to over 140 in 2020. The combination of the proton beam and a VEGF inhibitor, bevacizumab, decreased cell survival, increased apoptosis levels, and cell cycle arrest in melanoma cells [ 96 ]. The EGFR inhibitor gefitinib preferentially sensitized non-small cell lung cancer cells (H460 and H1299) to proton radiation compared to gamma radiation [ 97 ].…”