RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Synergistic anticancer effects of interleukin-21 combined with therapeutic peptides in multiple cancer cells.
Synergistic anticancer effects of interleukin-21 combined with therapeutic peptides in multiple cancer cells.
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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。
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。
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.
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