Cancer-associated fibroblasts treated with cisplatin facilitates chemoresistance of lung adenocarcinoma through IL-11/IL-11R/STAT3 signaling pathway.
Cancer-associated fibroblasts treated with cisplatin facilitates chemoresistance of lung adenocarcinoma through IL-11/IL-11R/STAT3 signaling pathway.
复制标题
顺铂治疗的癌症相关成纤维细胞通过IL-11/IL-11R/STAT3信号通路促进肺腺癌的化疗耐药
DOI：
10.1038/srep38408
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发表时间：
2016-12-06
影响因子：
4.6
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Tao L;Huang G;Wang R;Pan Y;He Z;Chu X;Song H;Chen L
癌症相关成纤维细胞（CAF）被认为是肺腺癌恶性进展的关键决定因素之一。其在肺癌化疗耐药获得中的作用越来越受到重视。在我们的研究中，用顺铂治疗的癌症相关成纤维细胞对肺癌细胞产生了化疗耐药。同时，白细胞介素-11（IL-11）在顺铂刺激的CAF中显著上调。在肺腺癌细胞的体内和体外实验中证实，IL-11可以保护顺铂诱导的癌细胞凋亡，从而促进癌细胞的化疗耐药。此外，我们还观察到IL-11诱导STAT3磷酸化，增加癌细胞中抗凋亡蛋白Bcl-2和Survivin的表达。这种作用可以通过抑制STAT3磷酸化或沉默癌细胞中IL-11Rα的表达来消除。综上所述，化疗诱导的CAF中IL-11的上调通过激活IL-11R/STAT3抗凋亡信号通路促进肺腺癌细胞的化疗耐药。
Cancer-associated fibroblasts (CAF) are recognized as one of the key determinants in the malignant progression of lung adenocarcinoma. And its contributions to chemoresistance acquisition of lung cancer has raised more and more attention. In our study, cancer associated fibroblasts treated with cisplatin conferred chemoresistance to lung cancer cells. Meanwhile, Interleukin-11(IL-11) was significantly up-regulated in the CAF stimulated by cisplatin. As confirmed in lung adenocarcinoma cellsin vivoandin vitro, IL-11 could protect cancer cells from cisplatin-induced apoptosis and thus promote their chemoresistance. Furthermore, it was also observed that IL-11 induced STAT3 phosphorylation and increased anti-apoptotic protein Bcl-2 and Survivin expression in cancer cells. The effect could be abrogated by suppressing STAT3 phosphorylation or silencing IL-11Rα expression in cancer cells. In conclusion, chemotherapy-induced IL-11 upregulation in CAF promotes lung adenocarcinoma cell chemoresistance by activating IL-11R/STAT3 anti-apoptotic signaling pathway.
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影响因子：
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作者：
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通讯作者：
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