机构：[1]Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA[2]Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China
Cisplatin-resistant A549 and H157 (A549CisR and H157CisR) non-small cell lung cancer cells show increased stemness of cancer stem cells (CSCs) compared to their parental cells. We investigated whether interleukin-6 (IL-6) signaling contributes to this increased stemness in cisplatin-resistant cells. When A549CisR and H157CisR cells were treated with neutralizing IL-6 antibody, decreased cisplatin resistance was observed, whereas IL-6 treatment of parental cells resulted in increased cisplatin resistance. Expression of the CSC markers was significantly upregulated in IL-6-expressing scramble cells (in vitro) and scramble cell-derived tumor tissues (in vivo) after cisplatin treatment, but not in IL-6 knocked down (IL-6si) (in vitro) cells and in IL-6si cell-derived tumor tissues (in vivo), suggesting the importance of IL-6 signaling in triggering increased stemness during cisplatin resistance development. Hypoxia inducible factors (HIFs) were upregulated by IL-6 and responsible for the increased CSC stemness on cisplatin treatment. Mechanism dissection studies found that upregulation of HIFs by IL-6 was through transcriptional control and inhibition of HIF degradation. Treatment of HIF inhibitor (FM19G11) abolished the upregulation of CSC markers and increased sphere formations in IL-6 expressing cells on cisplatin treatment. In all, IL-6-mediated HIF upregulation is important in increasing stemness during cisplatin resistance development, and we suggest that the strategies of inhibiting IL-6 signaling or its downstream HIF molecules can be used as future therapeutic approaches to target CSCs after cisplatin treatment for lung cancer.
第一作者机构：[1]Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA[2]Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Radiation Oncology, James P. Wilmot Cancer Center, University of Rochester, 601 Elmwood Ave., Box 647, Rochester, New York 14642, USA.
推荐引用方式(GB/T 7714)：
Fuquan Zhang,Shanzhou Duan,Ying Tsai,et al.Cisplatin treatment increases stemness through upregulation of hypoxia-inducible factors by interleukin-6 in non-small cell lung cancer[J].CANCER SCIENCE.2016,107(6):746-54.doi:10.1111/cas.12937.
APA：
Fuquan Zhang,Shanzhou Duan,Ying Tsai,Peter C. Keng,Yongbing Chen...&Yuhchyau Chen.(2016).Cisplatin treatment increases stemness through upregulation of hypoxia-inducible factors by interleukin-6 in non-small cell lung cancer.CANCER SCIENCE,107,(6)
MLA：
Fuquan Zhang,et al."Cisplatin treatment increases stemness through upregulation of hypoxia-inducible factors by interleukin-6 in non-small cell lung cancer".CANCER SCIENCE 107..6(2016):746-54
