肿瘤坏死因子-α（TNF-α）是一种强有力的促炎症因子，在建立炎症和癌症之间复杂联系方面起着重要作用。根据许多研究，TNF-α促进了肿瘤细胞增殖、迁移、侵袭和血管生成。研究表明，另一种重要的炎症细胞因子的下游转录因子STAT3在不同肿瘤特别是结肠直肠癌发展和进展中发挥了显著作用。在本研究中，我们研究了TNF-α通过STAT3激活在结肠直肠癌细胞的增殖和凋亡中的作用。本研究使用HCT116细胞系作为人类结肠直肠癌细胞。主要的实验包括MTT实验、逆转录-聚合酶链式反应（RT-PCR）、流式细胞术分析和酶联免疫吸附实验（ELISA）。结果显示，与对照组相比，TNF-α显著增加了STAT3的磷酸化和与细胞增殖、生存和转移相关的所有STAT3靶基因的表达。此外，我们的数据显示，在存在TNF-α + STA-21的情况下，STAT3的磷酸化和靶基因的表达显著降低，与TNF-α治疗组相比，这表明基因表达的增加部分是由于TNF-α诱导的STAT3激活。另一方面，在存在TNF-α + IL-6R的情况下，STAT3的磷酸化和靶基因的mRNA水平部分降低，支持通过诱导肿瘤细胞产生IL-6的间接途径来激活TNF-α引起的STAT3的机制。鉴于日益增多的证据表明STAT3是炎症引起结肠癌的关键调节因子，我们的发现支持进一步研究STAT3抑制剂作为潜在的癌症治疗方法。©2023年该作者（作者）独家许可Springer-Verlag GmbH Germany部分Springer Nature。

Tumor necrosis factor-alpha (TNF-α) is a potent pro-inflammatory factor that plays an important role in establishing a complicated connection between inflammation and cancer. TNF-α promotes tumor proliferation, migration, invasion, and angiogenesis according to numerous studies. Studies have shown the significant role of STAT3, a downstream transcription factor of another important inflammatory cytokine, IL-6 in the development and progression of different tumors especially colorectal cancer. In the present study, we investigated whether TNF-α has a role in proliferation and apoptosis of colorectal cancer cells through STAT3 activation. HCT116 cell line as human colorectal cancer cells was used in this study. Major assays were MTT assay, reverse transcription-PCR (RT-PCR), flow cytometric analysis, and ELISA. Results showed that TNF-α significantly increased the phosphorylation of STAT3 and expression of all the STAT3 target genes related to cell proliferation, survival, and metastasis compared with control. Moreover, our data showed that the STAT3 phosphorylation and expression of its target genes significantly were reduced in the presence of TNF-α + STA-21 compared with TNF-α-treated group demonstrating that the increase in genes expression partially was due to the TNF-α-induced STAT3 activation. On the other hand, STAT3 phosphorylation and mRNA levels of its target genes were partially decreased in the presence of TNF-α + IL-6R supporting the indirect pathway of STAT3 activation by TNF-α through inducing IL-6 production in cancer cells. Given the growing evidence for STAT3 as a key mediator of inflammation-induced colon cancer, our findings support further investigation of STAT3 inhibitors as potential cancer therapies.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.