Scholarlink

Abstract <p><b>Objective:</b> Tumor cell death induction via activation of TRAIL (tumor necrosis factor-related apoptosis inducing ligand) cytokine signaling pathway is a promising strategy for anticancer therapy. Previously, we developed a fusion protein SRH-DR5-B-iRGD based on the DR5 (death receptor 5)-specific cytokine TRAIL variant DR5-B with antiangiogenic peptides. The SRH peptide specifically binds to the VEGFR2 (vascular endothelial growth factor receptor 2) receptor and blocks its VEGF-mediated activation; the iRGD peptide binds to integrin αvβ3 and the NRP-1 (neuropilin-1) receptor. All of these targets are known to be overexpressed on the surface of tumor cells. In the current study, we investigated the cytotoxic activity of the SRH-DR5-B-iRGD fusion protein in comparison with DR5-B <i>in vitro</i> in ovarian and breast adenocarcinoma cell lines with different <i>BRCA</i> mutation status in combination with olaparib, a targeted poly(ADP-ribose) polymerase (PARP) inhibitor. <b>Methods:</b> Target receptor expression and correlation analysis were performed using the online tool TNMplot. Recombinant proteins DR5-B and SRH-DR5-B-iRGD were obtained in <i>Escherichia coli</i>. Cell viability was studied by MTT assay. <b>Results and Discussion:</b> Olaparib synergistically enhanced cytotoxicity of TRAIL-based proteins regardless of the cells’ <i>BRCA</i> mutation status. Importantly, this effect was more pronounced for SRH-DR5-B-iRGD. <b>Conclusions:</b> The combination of SRH-DR5-B-iRGD with olaparib can be considered as a new approach for the treatment of ovarian and breast adenocarcinoma regardless of their <i>BRCA</i> mutation status.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Combined Effects of Cytokine TRAIL-Based DR5-Specific Fusion Protein with Olaparib on Tumor Cell Lines with Different BRCA Mutation Status

  • 期刊论文

  • 发表日期：

    2025年6月3日

查看全文
  • A. V. Yagolovich,
  • A. A. Isakova,
  • E. V. Kukovyakina,
  • D. A. Dolgikh,
  • M. P. Kirpichnikov,
  • M. E. Gasparian

摘要

Abstract

Objective: Tumor cell death induction via activation of TRAIL (tumor necrosis factor-related apoptosis inducing ligand) cytokine signaling pathway is a promising strategy for anticancer therapy. Previously, we developed a fusion protein SRH-DR5-B-iRGD based on the DR5 (death receptor 5)-specific cytokine TRAIL variant DR5-B with antiangiogenic peptides. The SRH peptide specifically binds to the VEGFR2 (vascular endothelial growth factor receptor 2) receptor and blocks its VEGF-mediated activation; the iRGD peptide binds to integrin αvβ3 and the NRP-1 (neuropilin-1) receptor. All of these targets are known to be overexpressed on the surface of tumor cells. In the current study, we investigated the cytotoxic activity of the SRH-DR5-B-iRGD fusion protein in comparison with DR5-B in vitro in ovarian and breast adenocarcinoma cell lines with different BRCA mutation status in combination with olaparib, a targeted poly(ADP-ribose) polymerase (PARP) inhibitor. Methods: Target receptor expression and correlation analysis were performed using the online tool TNMplot. Recombinant proteins DR5-B and SRH-DR5-B-iRGD were obtained in Escherichia coli. Cell viability was studied by MTT assay. Results and Discussion: Olaparib synergistically enhanced cytotoxicity of TRAIL-based proteins regardless of the cells’ BRCA mutation status. Importantly, this effect was more pronounced for SRH-DR5-B-iRGD. Conclusions: The combination of SRH-DR5-B-iRGD with olaparib can be considered as a new approach for the treatment of ovarian and breast adenocarcinoma regardless of their BRCA mutation status.