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

BackgroundInterleukin-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.ObjectivesThis study aimed to compare the anticancer potential of IL-21 and IL-21 fusion proteins.MethodsAntimicrobial 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.ResultsThe 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.ConclusionFusion technology is a promising therapeutic technique that can be used to enhance the cytotoxicity and antiproliferative activity of anticancer proteins such as IL-21.