Comparative Evaluation of Therapeutic Efficacy of Radiotherapy, Bevacizumab, Calcidiol, and Calcitriol in Primary Uveal Melanoma Cell Line

Project no. 23029 · Status: Kapanmış · 2021

Summary

PURPOSE:To compare the therapeutic effects of radiotherapy (RT), 25-hydroxyvitamin D3 (D2), 1a,25-dihydroxyvitamin D3 (D3) and bevacizumab in primary uveal melanoma (UM) cell line.METHOD: In this study, the effects of RT, which is the classical treatment method, and D2, D3, bevacizumab agents alone and adjuvant on MP41 UM cell line were investigated. After proliferation and Inhibitory Concentration (IC50) analysis; D2, D3, bevacizumab were applied alone or in combination with RT, and the effect on proliferation was examined. Apoptosis with Annexin V/PI staining and cell cycle analyzes were performed. The effects of RT on colony formation were investigated.RESULTS: D2 and D3 did not show any toxic effect, the study was continued with 10 and 100 nM. The 48th hour IC50 for bevacizumab was 6.945 mg/ml. In the colony formation analysis, 3 Gy RT reduced the number of colonies by 50%. Analyzes were continued with this dose. RT and bevacizumab reduced cell proliferation in a dose-dependent manner when administered alone. D2 did not affect proliferation, while D3 moderately increased it. In combination with RT, 10 and 100 nM D2 and 10 nM D3 reduced the effect of RT, and 100 nM D3 had a proliferative effect. Bevacizumab increased the effect of RT in a dose-dependent manner. In the apoptosis analysis, the rate of viable cells in the control group was 94.6%, while it was dose-dependently reduced to 64.7% in the RT group. In the viable cell ratio, while there was no significant difference with 10 nM D2 and D3 (90.8%, 89.6%, respectively); decreasing was detected with 100 nM D2 and D3. A dose-dependent decrease was observed with bevacizumab, but this trend was impaired at 5 mg/ml (88%). Similar results were obtained with monotherapy in combined administration. In cell cycle analyzes, it was determined that D2 and D3 did not change the distribution, while bevacizumab moderately increased G2/M dominance in both monotheapy and adjuvant applications.CONCLUSION: This study is the first in the literature to investigate the effects of RT, D2, D3, and bevacizumab on the MP41 UM cell line. Bevacizumab is effective in inhibiting proliferation on the cell line. In addition, it has an additive effect when applied in combination with RT. The findings can shed light on clinical studies. In preclinical studies examining the effect of vitamin D on UM, the results are inconsistent and more studies are needed.

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