Cyclosporine A sensitizes human non-small cell lung cancer cells to gefitinib through inhibition of STAT3

被引：55

作者：

Shou, Jiawei ^{[1
]}

You, Liangkun ^{[1
]}

Yao, Junlin ^{[1
]}

Xie, Jiansheng ^{[2
]}

Jing, Jing ^{[3
]}

Jing, Zhao ^{[1
]}

Jiang, Liming ^{[1
]}

Sui, Xinbing ^{[1
]}

Pan, Hongming ^{[1
]}

Han, Weidong ^{[1
]}

机构：

[1] Zhejiang Univ, Sir Run Run Shaw Hosp, Coll Med, Dept Med Oncol, Hangzhou, Zhejiang, Peoples R China

[2] Zhejiang Univ, Sir Run Run Shaw Hosp, Coll Med, Inst Clin Sci,Lab Canc Biol, Hangzhou, Zhejiang, Peoples R China

[3] Tongde Hosp Zhejiang Prov, Dept Med Oncol, Hangzhou, Zhejiang, Peoples R China

来源：

CANCER LETTERS | 2016年 / 379卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Cyclosporine A; EGFR-TKI; Lung cancer; STAT3; ACQUIRED-RESISTANCE; GROWTH; EGFR; ERLOTINIB; PATHWAY; ACTIVATION; APOPTOSIS; CALCINEURIN; PACLITAXEL; LEUKEMIA;

D O I：

10.1016/j.canlet.2016.06.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

引用

页码：124 / 133

页数：10