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.

肿瘤坏死因子-α (TNF-α) 是一种有效的促炎因子，在建立炎症与癌症之间的复杂联系中起着重要作用。根据大量研究，TNF-α 促进肿瘤增殖、迁移、侵袭和血管生成。研究表明，STAT3 是另一种重要炎症细胞因子 IL-6 的下游转录因子，在不同肿瘤尤其是结直肠癌的发生发展过程中发挥着重要作用。在本研究中，我们研究了 TNF-α 是否通过 STAT3 激活在结直肠癌细胞的增殖和凋亡中发挥作用。HCT116 细胞系作为人结直肠癌细胞用于该研究。主要测定是 MTT 测定、逆转录-PCR (RT-PCR)、流式细胞术分析和 ELISA。结果表明，与对照相比，TNF-α 显着增加了 STAT3 的磷酸化以及所有与细胞增殖、存活和转移相关的 STAT3 靶基因的表达。此外，我们的数据显示，与 TNF-α 处理组相比，在 TNF-α + STA-21 存在的情况下，STAT3 磷酸化和其靶基因的表达显着降低，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 TNF-α + IL-6R 存在的情况下，STAT3 磷酸化及其靶基因的 mRNA 水平部分降低，支持 TNF-α 通过诱导癌细胞产生 IL-6 间接激活 STAT3 途径。鉴于越来越多的证据表明 STAT3 是炎症诱导的结肠癌的关键介质，