Although first-line chemotherapy drugs, including 5-fluorouracil (5-FU), remain one of the major choice for cancer treatment, the clinical use is also accompanied with dose-depending toxicities, such as intestinal mucositis (IM), in cancer patients undergoing treatment. IM-induced gastrointestinal adverse reactions become frequent reason to postpone chemotherapy and have negative impacts on therapeutic outcomes and prognosis. Various studies have evidenced the anticancer role of curcumin in many cancers; except for this effect, studies also indicated a protective role of curcumin in intestinal diseases. Therefore, in this study, we investigated the effect of curcumin on inflammation, intestinal epithelial cell damage in an IM model. 5-FU was used to induce the model of IM in intestinal epithelial cells, and curcumin at different concentrations was administrated. The results showed that curcumin efficiently attenuated 5-FU-induced damage to IEC-6 cells, inhibited the levels of inflammatory cytokines, attenuated the 5-FU-induced inhibition on cell viability, and displayed antiapoptosis effect on IEC-6 cells. Further RNA-sequencing analysis and experiment validation found that curcumin displays its protective effect against 5-FU-induced IM in intestinal epithelial cells by the inhibition of IL-6/STAT3 signaling pathway. Taken together, these findings suggested that curcumin may be provided as a therapeutic agent in prevention and treatment of chemotherapy-induced IM.

中文翻译：

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RNA-seq 和体外实验揭示姜黄素通过 IL-6/STAT3 信号通路对 5-氟尿嘧啶诱导的肠粘膜炎的保护作用

尽管包括 5-氟尿嘧啶 (5-FU) 在内的一线化疗药物仍然是癌症治疗的主要选择之一，但临床使用也伴随着剂量依赖的毒性，如癌症患者的肠粘膜炎 (IM)正在接受治疗。IM 引起的胃肠道不良反应成为推迟化疗的常见原因，并对治疗结果和预后产生负面影响。各种研究已经证明姜黄素在许多癌症中的抗癌作用。除了这种作用，研究还表明姜黄素在肠道疾病中具有保护作用。因此，在本研究中，我们在 IM 模型中研究了姜黄素对炎症、肠上皮细胞损伤的影响。5-FU用于诱导肠上皮细胞IM模型，并给予不同浓度的姜黄素。结果表明姜黄素能有效减轻5-FU诱导的IEC-6细胞损伤，抑制炎性细胞因子的水平，减弱5-FU诱导的细胞活力抑制，并显示出对IEC-6细胞的抗凋亡作用。进一步的 RNA 测序分析和实验验证发现，姜黄素通过抑制 IL-6/STAT3 信号通路显示其对 5-FU 诱导的肠上皮细胞 IM 的保护作用。总之，这些发现表明姜黄素可作为预防和治疗化学疗法诱发的 IM 的治疗剂。减弱了 5-FU 对细胞活力的抑制，并对 IEC-6 细胞显示出抗凋亡作用。进一步的 RNA 测序分析和实验验证发现，姜黄素通过抑制 IL-6/STAT3 信号通路显示其对 5-FU 诱导的肠上皮细胞 IM 的保护作用。总之，这些发现表明姜黄素可作为预防和治疗化学疗法诱发的 IM 的治疗剂。减弱了 5-FU 对细胞活力的抑制，并对 IEC-6 细胞显示出抗凋亡作用。进一步的 RNA 测序分析和实验验证发现，姜黄素通过抑制 IL-6/STAT3 信号通路显示其对 5-FU 诱导的肠上皮细胞 IM 的保护作用。总之，这些发现表明姜黄素可作为预防和治疗化学疗法诱发的 IM 的治疗剂。