期刊
GROWTH FACTORS
卷 41, 期 3, 页码 140-151出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/08977194.2023.2227271
关键词
Aflibercept; VEGF-Trap fusion protein; everolimus; lenvatinib; sorafenib
This study aimed to produce a biosimilar version of aflibercept (AFL) and evaluate its effect when used in combination with other vascular endothelial growth factor (VEGF) blocker drugs. The biosimilar-AFL showed significant inhibition potential on HUVEC cells in a dose-dependent manner. Furthermore, co-treatment with Everolimus (EVR), Lenvatinib (LEN), and Sorafenib (SOR) enhanced the cytotoxicity of biosimilar-AFL on HUVEC cells, with LEN and SOR showing a 10-fold increase in cytotoxicity. The combination of biosimilar-AFL with LEN showed the most efficient result, while the combination with EVR showed the least efficient result. Overall, biosimilar-AFL may improve the efficacy of LEN, EVR, and SOR in reducing the VEGF effect on endothelial cells.
This project aimed to produce a biosimilar version of aflibercept (AFL) and evaluate the effect of the co-treatment of AFL with other vascular endothelial growth factor (VEGF) blocker drugs. For this purpose, the optimized gene was inserted into the pCHO1.0 plasmid and transfected into the CHO-S cell line. The final concentration of biosimilar-AFL for the selected clone was 782 mg/L. Results revealed that the inhibition potential of the biosimilar-AFL on HUVEC cells was significant at 10 and 100 nM concentrations and in a dose-dependent manner. Furthermore, co-treatment of biosimilar-AFL with Everolimus (EVR), Lenvatinib (LEN), and Sorafenib (SOR) could reduce HUVEC cell viability/proliferation, more than when used alone. When LEN and SOR were co-treated with biosimilar-AFL, their cytotoxicity increased 10-fold. The most and least efficient combination was seen when biosimilar-AFL combined with LEN and EVR, respectively. Finally, biosimilar-AFL may improve the efficiency of LEN, EVR, and SOR in reducing the VEGF effect on endothelial cells.
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