Heze Municipal Hospital of Shandong Province, No 2888 Caozhou West Road, Heze 274000, Shandong, China.
Shanxian Central Hospital of Shandong Province, No 1 Wenhua Road, Shancheng town, Shanxian county 274300, Shandong, China.
Pathog Dis. 2019 Mar 1;77(2). doi: 10.1093/femspd/ftz019.
We aimed to investigate the relationship of intestinal dysbiosis (IDB) and ovarian cancer progression, and understand its underlying signaling mechanisms. IDB was induced with high dose antibiotics. The xenograft mouse model was used to assess the tumor progression. Real-time polymerase chain reaction and immunoblotting are commonly used quantitative methods, and they were used to quantify epithelial-mesenchymal transition (EMT) markers in this paper. Meanwhile, cellular proliferation was also measured. First, IDB could promote the growth of xenograft tumors and induce the EMT. Serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 also increased remarkably. In addition, the production and secretion of TNF-α and IL-6 in macrophages isolated from IDB model mice were observably higher. In vitro, conditioned medium could significantly stimulate the development of EMT in ovarian cancer cells. Loss of macrophages completely offset the pro-tumor effects of IDB. IDB can stimulate the activation of tumor-associated macrophages in ovarian cancer, which is achieved by secreting pro-inflammatory cytokines IL-6 and TNF-α, and ultimately induces the development of EMT.
本研究旨在探讨肠道菌群失调（IDB）与卵巢癌进展的关系，并深入了解其潜在的信号机制。通过大剂量抗生素诱导 IDB，利用异种移植小鼠模型评估肿瘤进展。实时聚合酶链反应和免疫印迹常用于定量分析 EMT 标志物，本文也采用了这两种方法。同时，还测量了细胞增殖情况。结果表明，IDB 可促进异种移植肿瘤生长并诱导上皮-间充质转化（EMT），肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6 血清水平也显著升高。此外，从 IDB 模型小鼠分离的巨噬细胞中 TNF-α和 IL-6 的产生和分泌明显增加。体外实验中，条件培养基可显著刺激卵巢癌细胞 EMT 的发展。巨噬细胞缺失完全抵消了 IDB 的促肿瘤作用。IDB 可通过分泌促炎细胞因子 IL-6 和 TNF-α刺激卵巢癌相关巨噬细胞的激活，进而诱导 EMT 的发生。
