期刊
CANCER LETTERS
卷 454, 期 -, 页码 37-43出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2019.04.002
关键词
Chemoresistance; Cancer-associated fibroblast; IL-8; NF-kappa B; ABCB1
类别
资金
- National Natural Science Foundation of China [81272711, 81871959]
- Priority Academic Program Development of Jiangsu Higher Education Institutions of Jiangsu Higher Education Institutions [JX10231801]
- Key Medical Talents Program of Jiangsu Province [ZDRCA2016014]
- Key R&D Program of Jiangsu Province [BE2018758]
- Programs of Jiangsu Province Hospital of Chinese Medicine [Y2018RC14, Y2018CX71]
Chemoresistance remains the major obstacle to achieve optimal prognosis in gastric cancer patients, and the underlying molecular mechanisms of cancer-associated fibroblasts (CAFs) in gastric cancer chemoresistance remain poorly understood. We identified the high pretherapeutical serum IL-8 level in gastric cancer patients was associated with poor response to platinum-based therapy, and it increased gradually during neoadjuvant chemotherapy and it decreased after radical surgery. Immunohistochemistry assays showed that IL-8 was highly expressed in gastric cancer tissues in chemoresistant patients, and located in CAFs. Primary CAFs produced more IL-8 than the corresponding normal fibroblasts, and human stomach fibroblast line Hs738 secreted more IL-8 after co-cultured with conditioned media from AGS or MGC-803 cells. IL-8 increased the IC50 of cisplatin (CDDP) in AGS or MGC-803 in vitro. Simultaneously, IL-8 treatment enhanced the expression of PI3K, phosphorylated-AKT (p-AKT), phosphorylated-IKb (p-IKb), phosphorylated-p65 (p-p65) and ABCB1, and ABCB1 and p-p65 were overexpressed in tumor tissues of chemoresistant patients. Collectively, CAFs derived IL-8 promotes chemoresistance in human gastric cancer via NF-kappa B activation and ABCB1 up-regulation. Our study provides a novel strategy to improve the chemotherapeutical efficacy and the prognosis of gastric cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据