1. Academic Validation
  2. A high-throughput drug screen identifies auranofin as a potential sensitizer of cisplatin in small cell lung cancer

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

  • Invest New Drugs. 2019 Dec;37(6):1166-1176. doi: 10.1007/s10637-019-00750-2.
Xiaoli Liu 1 2 3 Wei Wang 1 3 Yanping Yin 1 2 3 Ming Li 1 2 3 Hong Li 1 3 Hang Xiang 1 2 3 Ao Xu 4 Xiaodong Mei 4 Bo Hong 5 6 Wenchu Lin 7 8
Affiliations

Affiliations

  • 1 High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, 230031, Anhui, People's Republic of China.
  • 2 University of Science and Technology of China, Hefei, 230036, Anhui, People's Republic of China.
  • 3 Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, Anhui, People's Republic of China.
  • 4 The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People's Republic of China.
  • 5 High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, 230031, Anhui, People's Republic of China. [email protected].
  • 6 Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, Anhui, People's Republic of China. [email protected].
  • 7 High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, 230031, Anhui, People's Republic of China. [email protected].
  • 8 Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, Anhui, People's Republic of China. [email protected].
Abstract

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

Auranofin; Ciplatin; DNA damage; ROS; Small cell lung cancer.

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