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新型融合裂解肽靶向表达白细胞介素-13 受体 (IL-13R)α2 的前列腺癌。

Targeting of the Interleukin-13 Receptor (IL-13R)α2 Expressing Prostate Cancer by a Novel Hybrid Lytic Peptide.

机构信息

UCL ECMC GCLP Facility, UCL Cancer Institute, University College London, London WC1E 6DD, UK.

Institute of Life Science, School of Medicine, Swansea University, Singleton Park, Swansea SA2 8PP, UK.

出版信息

Biomolecules. 2023 Feb 12;13(2):356. doi: 10.3390/biom13020356.

DOI:10.3390/biom13020356
PMID:36830725
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9953383/
Abstract

The IL-13Rα2 cell surface receptor is highly expressed in tumours such as prostate cancer. In this report, we evaluated the hypothesis that prostate cancer cells with enhanced IL-13Rα2 expression are a suitable target for the hybrid lytic peptide (Pep-1-Phor21) peptide, which is generated by fusing the IL-13Rα2 specific ligand (Pep-1) and a cell membrane disrupting lytic peptide (Phor21). The expression of IL-13Rα2 mRNA and protein in prostate cancer tissues and cell lines was assessed via real-time PCR (RT-PCR) and immunoblotting. The effect of Pep-1-Phor21 on the viability of prostate cancer cells grown in monolayers (2D) and microtissue spheroids (3D) was assessed via CellTox green cytotoxic assay. IL-13Rα2 expression and Pep-1-Phor21-mediated killing were also determined in the cells treated with epigenetic regulators (Trichostatin A (TSA) and 5-aza-2 deoxycytidine (5-Aza-dC)). The hybrid lytic peptide cytotoxic activity correlated with the expression of IL-13Rα2 in prostate cancer cell lines cultured as monolayers (2D) or 3D spheroids. In addition, TSA or 5-Aza-dC treatment of prostate cancer cells, particularly those with low expression of IL-13Rα2, enhanced the cells' sensitivity to the lytic peptide by increasing IL-13Rα2 expression. These results demonstrate that the Pep-1-Phor21 hybrid lytic peptide has potent and selective anticancer properties against IL-13Rα2-expressing prostate cancer cells.

摘要

白细胞介素 13 受体α2 细胞表面受体在前列腺癌等肿瘤中高度表达。在本报告中，我们评估了这样一种假设，即表达增强的白细胞介素 13 受体α2 的前列腺癌细胞是融合了白细胞介素 13 受体α2 特异性配体（Pep-1）和细胞膜破坏裂解肽（Phor21）的杂交裂解肽（Pep-1-Phor21）的合适靶标。通过实时 PCR（RT-PCR）和免疫印迹评估前列腺癌组织和细胞系中白细胞介素 13 受体α2 mRNA 和蛋白的表达。通过 CellTox green 细胞毒性测定评估 Pep-1-Phor21 对单层（2D）和微组织球体（3D）中生长的前列腺癌细胞活力的影响。还在经表观遗传调节剂（曲古抑菌素 A（TSA）和 5-氮杂-2-脱氧胞苷（5-Aza-dC））处理的细胞中确定了白细胞介素 13 受体α2 表达和 Pep-1-Phor21 介导的杀伤作用。杂交裂解肽的细胞毒性活性与前列腺癌细胞系在单层（2D）或 3D 球体中培养时白细胞介素 13 受体α2 的表达相关。此外，前列腺癌细胞，尤其是白细胞介素 13 受体α2 低表达的前列腺癌细胞，经 TSA 或 5-Aza-dC 处理后，通过增加白细胞介素 13 受体α2 的表达，增强了细胞对裂解肽的敏感性。这些结果表明，Pep-1-Phor21 杂交裂解肽对表达白细胞介素 13 受体α2 的前列腺癌细胞具有强大且选择性的抗癌特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/15dfaeca4ab3/biomolecules-13-00356-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/9cd43423add5/biomolecules-13-00356-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/1e7f419b0ee7/biomolecules-13-00356-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/f2c3db5e4be1/biomolecules-13-00356-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/f89e3ce16f15/biomolecules-13-00356-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/6696c1669051/biomolecules-13-00356-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/b79415af1fc4/biomolecules-13-00356-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/adf41180d931/biomolecules-13-00356-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/12a5382fa20f/biomolecules-13-00356-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/15dfaeca4ab3/biomolecules-13-00356-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/9cd43423add5/biomolecules-13-00356-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/1668c9de43df/biomolecules-13-00356-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/a9105f939c3a/biomolecules-13-00356-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/1e7f419b0ee7/biomolecules-13-00356-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/f2c3db5e4be1/biomolecules-13-00356-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/f89e3ce16f15/biomolecules-13-00356-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/6696c1669051/biomolecules-13-00356-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/b79415af1fc4/biomolecules-13-00356-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/adf41180d931/biomolecules-13-00356-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/12a5382fa20f/biomolecules-13-00356-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b2d/9953383/15dfaeca4ab3/biomolecules-13-00356-g011.jpg

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