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Investigational New Drugs

, Volume 37, Issue 6, pp 1166–1176 | Cite as

A high-throughput drug screen identifies auranofin as a potential sensitizer of cisplatin in small cell lung cancer

  • Xiaoli Liu
  • Wei Wang
  • Yanping Yin
  • Ming Li
  • Hong Li
  • Hang Xiang
  • Ao Xu
  • Xiaodong Mei
  • Bo HongEmail author
  • Wenchu LinEmail author
PRECLINICAL STUDIES

Summary

Small cell lung cancer (SCLC) is a highly lethal malignancy with the 5-year survival rate of less than 7%. Chemotherapy-resistance is a major challenge for SCLC treatment in clinic. In the study, we developed a high-throughput drug screen strategy to identify new drugs that can enhance the sensitivity of chemo-drug cisplatin in SCLC. This screen identified auranofin, a US Food and Drug Administration (FDA)-approved drug used therapeutically for rheumatoid arthritis, as a sensitizer of cisplatin. Further study validated that auranofin synergistically enhanced the anti-tumor activity of cisplatin in chemo-resistant SCLC cells, which was accompanied by the enhanced induction of cell cycle arrest and apoptosis. The synergistic action of auranofin and cisplatin was through ROS overproduction, thereby leading to mitochondrial dysfunction and DNA damage. Furthermore, in vivo study demonstrated that the combination treatment of auranofin and cisplatin dramatically inhibited tumor growth in SCLC. Therefore, our study provides a rational basis for further clinical study to test whether auranofin could enhance the sensitivity of cisplatin-based therapy in SCLC patients.

Keywords

Small cell lung cancer Ciplatin Auranofin ROS DNA damage 

Abbreviations

SCLC

Small cell lung cancer

NSCLC

Non-small cell lung cancer

FDA

Food and Drug Administration

MMP

Mitochondrial membrane potential

CI

Combination index

Notes

Acknowledgements

This study was supported by National Natural Science Foundation of China (Grant Numbers: 81872438, 81672647, 81502632), Natural Science Foundation of Anhui Province (Grant Number: 1608085MH179), Science and Technology Major Project of Anhui Province (Grant Number: 18030801140), Science and Technology Service Network Initiative of Chinese Academy of Sciences (Grant Number: KFJ-STS-SCYD-010), Key program of 13th five-year plan of CASHIPS (Grant Number: KP-2017-26), and the 100-Talent Program of Chinese Academy of Sciences.

Funding

This study was supported by National Natural Science Foundation of China (Grant Numbers: 81872438, 81672647, 81502632), Natural Science Foundation of Anhui Province (Grant Number: 1608085MH179), Science and Technology Major Project of Anhui Province (Grant Number: 18030801140), Science and Technology Service Network Initiative of Chinese Academy of Sciences (Grant Number: KFJ-STS-SCYD-010), Key program of 13th five-year plan of CASHIPS (Grant Number: KP-2017-26), and the 100-Talent Program of Chinese Academy of Sciences..

Compliance with ethical standards

Conflict of interest

Authors have no financial/commercial conflicts of interest regarding the study.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

This article does not contain any studies with human participants performed by any of the authors.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.High Magnetic Field LaboratoryChinese Academy of SciencesHefeiPeople’s Republic of China
  2. 2.University of Science and Technology of ChinaHefeiPeople’s Republic of China
  3. 3.Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical ScienceChinese Academy of SciencesHefeiPeople’s Republic of China
  4. 4.The First Affiliated Hospital of USTC, Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiPeople’s Republic of China

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