Cyclosporine A sensitizes human non-small cell lung cancer cells to gefitinib through inhibition of STAT3
Authors: Liming Jiang
Jing Jing
Liangkun You
Zhao Jing
Weidong Han
Junlin Yao
Hongming Pan
Jiansheng Xie
Jiawei Shou
Xinbing Sui
Journal: Cancer Letters (2016)
Discipline: CLINICAL MEDICINE
Keywords: Cyclosporine A; EGFR–TKI; Lung cancer; STAT3.
Affiliations: Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China., Laboratory of Cancer Biology, Institute of Clinical Science, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China., Department of Medical Oncology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, China., Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address: .

Abstract:  The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have dramatically prolonged the overall survival of non-small cell lung cancer (NSCLC) patients with EGFR-activating mutation, but the presence of primary or acquired resistance eventually leads to therapeutic failure. Thus, how to improve the efficacy and reverse the resistance to EGFR-TKIs remains a significant challenge. In this study, we found that CsA significantly augmented the anti-cancer effect of gefitinib in EGFR-TKI-sensitive and -resistant NSCLC cells. Mechanistically, CsA promoted gefitinib-induced apoptosis through inhibition of the STAT3 pathway. Similar with the function of CsA, siRNAs against STAT3 also enhanced gefitinib-induced apoptosis in multiple lung cancer cells. Xenograft studies further demonstrated that CsA promoted the anti-cancer activity of gefitinib on lung cancer cells through inhibition of STAT3. Moreover, NSCLC patients with high levels of phosphorylated STAT3 (Y705) showed a significantly poorer therapeutic response to EGFR-TKIs. This study provides preclinical evidence that the combination of CsA or a STAT3 inhibitor with EGFR-TKIs is a promising approach to improve the efficacy of EGFR-TKIs for the treatment of patients with advanced NSCLC. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. Figure 3. Similarities between panels in Figure 3F and 3H. I am personally not certain about the ones marked in yellow, but I hope the authors can show the original, uncut blots. ![file] , 
 The same reader found similar looking panels (marked in red) in Supplementary Figure 6: ![file] They also found similar looking flow cytometry panels in Supplementary Figure 8 (also marked in red): ![file] , 
 We will investigate the issue thoroughly and will deal with it as soon as possible. , 
 We carefully checked the original data of the experiment and found that there were indeed some errors in processing figures. We are deeply sorry for this. We confirmed that these errors did not influence the statistical analysis, the overall results and conclusions of this article. We have contacted the editorial department to correct this problem. Thank you for your query. , 
 November 28, 2020 Correction, found here: https: www.sciencedirect.com science article pii S0304383520303773?via%3Dihub. It reads:  The authors regret to inform the readers that the stripes of t-STAT3 and GAPDH in Fig. 3H were mistakenly replaced by the stripes of t-STAT3 and GAPDH in Fig. 3F, respectively. Now the corrected Fig. 3H is displayed in Pic. 1. The images of FK506 line in Fig.S6H were mistakenly replaced by the images of Gef + CsA line in Fig.S6G in the Supplementary Fig.6. Now the corrected Fig.S6H is displayed in Pic. 2. The images of apoptosis in Fig.S8B were mistakenly replaced by the images of apoptosis in Fig.S8A in the Supplementary Fig.8. Now the corrected Fig.S8B is displayed in Pic. 3. The authors confirmed that this error did not influence the statistical analysis, the overall results and conclusions of this article. All authors are gratitude to this opportunity to rectify the record and agree with this correction. Additionally, the authors deeply apologize for any inconvenience caused. I was not notified of this correction. ,