title: Cancer-associated fibroblasts treated with cisplatin facilitates chemoresistance of lung adenocarcinoma through IL-11/IL-11R/STAT3 signaling pathway.
abstract: 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 cells in vivo and in 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.
authors.affiliation: Medical Oncology Department of Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002 People's Republic of China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Tao
authors.affiliation: Medical Oncology Department of Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002 People's Republic of China.
authors.forename: Guichun
authors.initials: G
authors.lastname: Huang
authors.affiliation: Medical Oncology Department of Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002 People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Medical Oncology Department of Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002 People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Medical Oncology Department of Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002 People's Republic of China.
authors.forename: Zhenyue
authors.initials: Z
authors.lastname: He
authors.affiliation: Medical Oncology Department of Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002 People's Republic of China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chu
authors.affiliation: Medical Oncology Department of Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002 People's Republic of China.
authors.forename: Haizhu
authors.initials: H
authors.lastname: Song
authors.affiliation: Medical Oncology Department of Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002 People's Republic of China.
authors.forename: Longbang
authors.initials: L
authors.lastname: Chen
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000072645:Cancer-Associated Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017370:Interleukin-11 / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010616:Phenanthrenes / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D053702:Receptors, Interleukin-11 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C508611:IL11 protein, human; D017370:Interleukin-11; D010616:Phenanthrenes; D034741:RNA, Small Interfering; D053702:Receptors, Interleukin-11; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C037886:cryptotanshinone; D002945:Cisplatin