Investigational New Drugs

, Volume 37, Issue 4, pp 616–624 | Cite as

Preclinical assessment of histone deacetylase inhibitor quisinostat as a therapeutic agent against esophageal squamous cell carcinoma

  • Lei Zhong
  • Shu Zhou
  • Rongsheng Tong
  • Jianyou Shi
  • Lan Bai
  • Yuxuan Zhu
  • Xingmei Duan
  • Wenzhao Liu
  • Jinku Bao
  • Lingyu SuEmail author
  • Qian PengEmail author


Esophageal squamous cell carcinoma (ESCC) is one of the most serious life-threatening malignancies. Although chemotherapeutic targets and agents for ESCC have made much progress recently, the efficacy is still unsatisfactory. Therefore, there is still an unmet medical need for patients with ESCC. Here, we report the expression status of HDAC1 in human ESCC and matched paracancerous tissues, and the results indicated that HDAC1 was generally upregulated in ESCC specimens. Furthermore, we comprehensively assessed the anti-ESCC activity of a highly active HDAC1 inhibitor quisinostat. Quisinostat could effectively suppress cellular viability and proliferation of ESCC cells, as well as induce cell cycle arrest and apoptosis even at low treatment concentrations. The effectiveness was also observed in KYSE150 xenograft model when quisinostat was administered at tolerated doses (3 mg/kg and 10 mg/kg). Meanwhile, quisinostat also had the ability to suppress the migration and invasion (pivotal steps of tumor metastasis) of ESCC cells. Western blot analysis indicated that quisinostat exerted its anti-ESCC effects mainly through blockade of Akt/mTOR and MAPK/ERK signaling cascades. Overall, HDAC1 may serve as a potential therapeutic target for ESCC, and quisinostat deserves to be further assessed as a promising drug candidate for the treatment of ESCC.


Esophageal squamous cell carcinoma Quisinostat Histone deacetylase Cancer therapy 


Author contributions

L Zhong and S Zhou contributed equally to this article.

Conception and design: L Zhong, S Zhou, LY Su, and Q Peng;

Development of methodology: L Zhong, S Zhou, and RS Tong;

Acquisition of data: L Zhong, S Zhou, and JY Shi;

Analysis and interpretation of data: L Zhong, RS Tong, and Q Peng;

Technical and material supports: YX Zhu, L Bai, XM Duan, WZ Liu, and JK Bao; Writing and review of the manuscript: L Zhong, S Zhou, LY Su, and Q Peng;

Study supervision: RS Tong, LY Su, and Q Peng.


This work was supported by the National Natural Science Foundation of China (81702286 and 81300882), the Fundamental Research Funds of Science & Technology Department of Sichuan Province (2017YSKY0001), and the Special Foundation for Young Scientists of Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital (2016QN11).

Compliance with ethical standards

Conflicts of interest

The authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the Animal Care and Use Committee of Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital (Chengdu, Sichuan, China).


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Personalized Drug Therapy Key Laboratory of Sichuan ProvinceSichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalChengduChina
  2. 2.School of Life Sciences and Key Laboratory of Bio-resources and Eco-environment, Ministry of EducationSichuan UniversityChengduChina
  3. 3.College of StomatologyChongqing Medical UniversityChongqingChina
  4. 4.Chongqing Key Laboratory for Oral Diseases and Biomedical ScienceChongqingChina
  5. 5.Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher EducationChongqingChina
  6. 6.Cancer CenterSichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalChengduChina

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