Feng-Liao-Chang-Wei-Kang Combined with 5-Fluorouracil Synergistically Suppresses Colitis-Associated Colorectal Cancer via the IL-6/STAT3 Signalling Pathway.
Feng-Liao-Chang-Wei-Kang Combined with 5-Fluorouracil Synergistically Suppresses Colitis-Associated Colorectal Cancer via the IL-6/STAT3 Signalling Pathway.
复制标题
风辽肠胃康联合5-氟尿嘧啶通过IL-6/STAT3信号通路协同抑制结肠炎相关结直肠癌
DOI：
10.1155/2020/1395954
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Huang L
中科院分区：
文献类型：
--
作者：
Zhong L;Yang F;Gan L;Yang Z;Tian S;Huang M;Lv C;Huang L
背景结肠炎相关结直肠癌（CAC）是由活动性结肠炎症发展而来的，其特征是产生可诱导突变的促炎细胞因子。IL-6由位于肿瘤微环境中的多种细胞类型产生，包括肿瘤浸润免疫细胞、基质细胞和肿瘤细胞本身。本研究旨在探讨蜂疗肠萎康联合5-氟尿嘧啶治疗CAC的作用机制。方法用5-FU处理HCT 116细胞，观察FLCWK对细胞增殖的影响。MTT法检测细胞增殖;流式细胞仪检测细胞凋亡和细胞周期时相。Western blotting和Q-PCR检测IL-6/STAT 3信号通路相关蛋白和基因的表达水平。通过用12.5mg/kg的氧化偶氮甲烷（AOM）处理动物，随后用2.5%的葡聚糖硫酸钠（DSS）处理3个周期，建立CAC的小鼠模型。苏木精-伊红（H&E）染色后测定相关的病理变化。用免疫荧光技术检测不同组织中相关蛋白和基因的表达。结果FLCWK通过抑制HCT 116细胞增殖和阻断IL-6/STAT 3通路，增强5-FU促凋亡的能力。FLCWK联合5-FU可减少CAC小鼠结肠肿瘤的数量和大小，并显着提高其生存率。在CAC模型中，FLCWK与5-FU协同抑制STAT 3的磷酸化，阻止IL-6/STAT 3信号转导，从而进一步诱导凋亡和抑制结肠癌细胞增殖。结论FLCWK可通过减少IL-6的产生，抑制STAT 3的活化，从而增加结肠炎相关大肠癌的发生。
Background Colitis-associated colorectal cancer (CAC) develops from active colonic inflammation, which is characterized by the production of proinflammatory cytokines that can induce mutations. IL-6 is produced by multiple cell types located within the tumor microenvironment including tumor-infiltrating immune cells, stromal cells, and the tumor cells themselves. The aim of our study was to explore the mechanism of Feng-Liao-Chang-Wei-Kang (FLCWK) and 5-fluorouracil (5-FU) in treating CAC. Method HCT116 cells were treated with 5-FU in the absence or presence of FLCWK. Cell proliferation was assayed by MTT assays. Apoptosis and the cell cycle phases were detected by flow cytometry. Western blotting and Q-PCR assays were used to detect the expression levels of proteins and genes related to the IL-6/STAT3 signalling pathway. A mouse model for CAC was established by treating animals with 12.5 mg/kg azoxymethane (AOM) followed by 3 cycles of 2.5% dextran sodium sulphate (DSS). The associated pathological changes were determined after haematoxylin and eosin (H&E) staining. The expression of related proteins and genes in various tissues was examined using immunofluorescence techniques. Results FLCWK enhanced the ability of 5-FU to promote apoptosis by inhibiting the proliferation of HCT116 cells and blocking the IL-6/STAT3 pathway. FLCWK combined with 5-FU reduced the number and size of colon tumors in mice with CAC and significantly increased their survival rate. In the CAC model, FLCWK synergized with 5-FU to inhibit the phosphorylation of STAT3, preventing IL-6/STAT3 signal transduction and thus further inducing apoptosis and inhibition of colon cancer cell proliferation. Conclusion FLCWK can inhibit the activation of STAT3 by reducing the production of IL-6, thereby increasing the occurrence of colitis-related colorectal cancer with 5-FU.
登录
查看更多内容
风抑肠胃康与5-氟尿嘧啶协同抑制结直肠癌增殖
影响因子：
3.1
作者：
Ni, Pan-li;Tian, Shu-hong;Huang, Ling
通讯作者：
Huang, Ling
影响因子：
8.8
作者：
Nagasaki, T.;Hara, M.;Nakanishi, H.;Takahashi, H.;Sato, M.;Takeyama, H.
通讯作者：
Takeyama, H.
影响因子：
15.9
作者：
Bromberg, J
通讯作者：
Bromberg, J
影响因子：
3.4
作者：
Lassmann, Silke;Schuster, Ingrid;Werner, Martin
通讯作者：
Werner, Martin
DOI：
10.4161/jkst.23828
发表时间：
2013-04-01
期刊：
JAK-STAT
影响因子：
--
作者：
Bournazou E;Bromberg J
通讯作者：
Bromberg J