Abdalkareem Eshtiyag Abdalla, Ong Ching Yi, Lim Boon Huat, Khoo Boon Yin
Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800, Penang, Malaysia.
Tropical Medicine Research Institute (TMRI), Khartoum, Sudan.
Cytotechnology. 2018 Oct;70(5):1363-1374. doi: 10.1007/s10616-018-0228-2. Epub 2018 May 25.
The interleukin-21 (IL-21) protein was found to be expressed at an elevated level in clinical samples of colorectal cancer patients without or with a parasitic infection that were collected from Sudan in our previous study. The IL-21 gene in HT29 and HCT116 cells was then correlated to cell proliferation and cell migration, as well as the cellular mechanisms associated with gene expressions in our present study. Our results demonstrated that silencing the IL-21 gene in HCT116 cells increased the cytotoxic level and fibroblast growth factor-4 (FGF4) mRNA expression in the cancer cells. Moreover, specific gene silencing reduced the migration of cancer cells compared to non-silenced cancer cells. These events were not observed in IL-21-silenced HT29 cells. Neutralizing FGF4 in conditioned medium of IL-21-silenced HCT116 cells further increased the cytotoxic level and restored the migratory activity of HCT116 cells in the culture compared to silencing the IL-21 gene alone in the cancer cells. Our results indicate the importance of both silencing the IL-21 gene and co-expression of the FGF4 protein in HCT116 cells, which pave the way for the discovery of important factors to be used as biomarkers for the design of drugs or cost-effective supplements to effectively treat the patients having infectious disease and HCT116 cells of colorectal cancer simultaneously in the future.
在我们之前的研究中,发现白细胞介素-21(IL-21)蛋白在从苏丹收集的未感染或感染寄生虫的结直肠癌患者临床样本中表达水平升高。在本研究中,HT29和HCT116细胞中的IL-21基因与细胞增殖、细胞迁移以及与基因表达相关的细胞机制相关。我们的结果表明,沉默HCT116细胞中的IL-21基因会增加癌细胞的细胞毒性水平和成纤维细胞生长因子-4(FGF4)mRNA表达。此外,与未沉默的癌细胞相比,特异性基因沉默降低了癌细胞的迁移。在IL-21沉默的HT29细胞中未观察到这些现象。与仅在癌细胞中沉默IL-21基因相比,中和IL-21沉默的HCT116细胞条件培养基中的FGF4进一步提高了细胞毒性水平,并恢复了培养物中HCT116细胞的迁移活性。我们的结果表明,沉默IL-21基因和FGF4蛋白在HCT116细胞中的共表达都很重要,这为发现重要因素作为生物标志物铺平了道路,以便将来设计药物或具有成本效益的补充剂,从而有效治疗同时患有传染病和结直肠癌HCT116细胞的患者。