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

IF 2 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Biotechnology Letters Pub Date : 2024-11-28 DOI:10.1007/s10529-024-03544-6

Muhammad Akram, Nao Akusa Fujimura, Saad Tahir, Rabia Abbas, Mohsin Ahmad Khan, Kausar Malik, Nadeem Ahmed

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Abstract

Background: 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.

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

Methods: 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.

Results: 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.

Conclusion: 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.

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白细胞介素-21联合治疗肽对多种癌细胞的协同抗癌作用。

背景：白细胞介素-21 （IL-21）是一种由T细胞、自然杀伤细胞、骨髓细胞和B细胞等多种细胞类型产生的细胞因子，在癌症治疗中具有广泛的潜在应用前景。为了提高治疗指数，我们探索了融合技术的使用，包括使用特定的连接物将其他抗癌肽连接到IL-21基因。目的：比较IL-21与IL-21融合蛋白的抗癌作用。方法：利用柔性连接体（- ggggs -）将具有抗癌特性的抗菌肽与IL-21基因融合，并将其插入pSecTag2a哺乳动物表达载体中。将该磁带转染到包括H1 - HeLa、HepG2、MCF-7、MDA-MB-231、HCT-116、HCC-1954、HEK-293和SF-767在内的几种癌细胞系中。采用MTT、Caspase-3、LDH和划痕法评估IL-21和融合蛋白的细胞毒性作用。结果：IL-21- tachyplesin I融合蛋白对所有肿瘤细胞的抗增殖活性最强，其次是IL-21- lpsbd2和IL-21。相比之下，IL21-Cop A3、IL21-CSP I-Plus和IL21-RGD Temporin-Las没有抑制癌细胞的活性。结论：融合技术可提高IL-21等抗癌蛋白的细胞毒性和抗增殖活性，是一种很有前景的治疗技术。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biotechnology Letters 工程技术-生物工程与应用微生物

CiteScore

5.90

自引率

3.70%

发文量

108

审稿时长

1.2 months

期刊介绍： Biotechnology Letters is the world’s leading rapid-publication primary journal dedicated to biotechnology as a whole – that is to topics relating to actual or potential applications of biological reactions affected by microbial, plant or animal cells and biocatalysts derived from them. All relevant aspects of molecular biology, genetics and cell biochemistry, of process and reactor design, of pre- and post-treatment steps, and of manufacturing or service operations are therefore included. Contributions from industrial and academic laboratories are equally welcome. We also welcome contributions covering biotechnological aspects of regenerative medicine and biomaterials and also cancer biotechnology. Criteria for the acceptance of papers relate to our aim of publishing useful and informative results that will be of value to other workers in related fields. The emphasis is very much on novelty and immediacy in order to justify rapid publication of authors’ results. It should be noted, however, that we do not normally publish papers (but this is not absolute) that deal with unidentified consortia of microorganisms (e.g. as in activated sludge) as these results may not be easily reproducible in other laboratories. Papers describing the isolation and identification of microorganisms are not regarded as appropriate but such information can be appended as supporting information to a paper. Papers dealing with simple process development are usually considered to lack sufficient novelty or interest to warrant publication.