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白细胞介素-21 联合治疗性肽在多种癌细胞中的协同抗癌作用

英文原题:Synergistic anticancer effects of interleukin-21 combined with therapeutic peptides in multiple cancer cells.

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Synergistic anticancer effects of interleukin-21 combined with therapeutic peptides in multiple cancer cells.

PubMed 2024/11/28(内容时间) Biotechnol Lett Q3 · IF 2.5(JCR 2025)

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研究概要

融合技术是一种有前景的治疗技术,可用于增强抗癌蛋白如 IL-21 的细胞毒性和抗增殖活性。

研究思路结论见上方概要

白细胞介素-21(IL-21)是一种由多种细胞类型产生的细胞因子,包括T细胞、NK 细胞、髓系细胞和B细胞,在癌症治疗中具有广泛的潜在应用。为了提高治疗指数,我们探索了融合技术的使用,该技术涉及使用特定连接子将其他抗癌肽与IL-21基因连接。

本研究旨在比较IL-21和IL-21融合蛋白的抗癌潜力。

具有抗癌特性的抗菌肽通过柔性连接肽(-GGGGS-)与IL-21基因融合,所得构建体插入pSecTag2a哺乳动物表达载体。该表达盒转染至多种癌细胞系,包括H1 HeLa、HepG2、MCF-7、MDA-MB-231、HCT-116、HCC-1954、HEK-293和SF-767。采用MTT、Caspase-3、LDH和划痕实验评估IL-21及融合蛋白的细胞毒性作用。

IL-21-Tachyplesin I融合蛋白对所有测试的癌细胞具有最强的抗增殖活性,其次是IL21-LPSBD2和IL-21。相比之下,IL21-Cop A3、IL21-CSP I-Plus和IL21-RGD Temporin-Las未抑制癌细胞的活力。

展开英文摘要原文

Interleukin-21 (IL-21) is a cytokine produced by various cell types, including T cells, natural killer cells, myeloid cells, and B cells, and has a broad range of potential applications in cancer therapy. To improve the therapeutic index, we explored the use of fusion technologies that involved linking other anticancer peptides to the IL-21 gene using specific linkers.

This study aimed to compare the anticancer potential of IL-21 and IL-21 fusion proteins.

Antimicrobial peptides possessing anticancer properties were fused with IL-21 gene using a flexible linker (-GGGGS-), and the resulting construct was inserted into the pSecTag2a mammalian expression vector. The cassette was transfected into several cancer cell lines including H1 HeLa, HepG2, MCF-7, MDA-MB-231, HCT-116, HCC-1954, HEK-293, and SF-767. The cytotoxic effects of IL-21 and fusion proteins were evaluated using MTT, Caspase-3, LDH, and scratch assays.

The IL-21-Tachyplesin I fusion protein had the strongest antiproliferative activity against all tested cancer cells, followed by IL21-LPSBD2 and IL-21. In contrast, IL21-Cop A3, IL21-CSP I-Plus, and IL21-RGD Temporin-Las did not inhibit the viability of cancer cells.

Fusion technology is a promising therapeutic technique that can be used to enhance the cytotoxicity and antiproliferative activity of anticancer proteins such as IL-21.

论文信息

作者
Akram M、Fujimura NA、Tahir S、Abbas R、Khan MA、Malik K、Ahmed N
第一作者单位
Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan.Pakistan
通讯作者单位
Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan. nadeem.ahmed@cemb.edu.pk.Pakistan
期刊
Biotechnology letters2024 Nov 28
原文标识
PubMed 39609311 · DOI 10.1007/s10529-024-03544-6