Histone deacetylases inhibitor MS-275 suppresses human esophageal squamous cell carcinoma cell growth and progression via the PI3K/Akt/mTOR pathway

Shanshan Ma, Tengfei Liu, Ling Xu, Yaping Wang, Jiankang Zhou, Tuanjie Huang, Peng Li, Hongtao Liu, Yanting Zhang, Xinkui Zhou, Yuanbo Cui, Xingxing Zang, Yuming Wang, Fangxia Guan

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with low survival rate, so new therapies are urgently needed. Histone deacetylases (HDACs) play a critical role in tumorigenesis, and HDACs inhibition is a potential therapeutic target in ESSC. In our study, we evaluated the effect and molecular mechanism of MS-275 (an inhibitor of HDACs) on ESCC cells. We found that HDAC1 and HDAC2 were overexpressed in ESCC tissues and related with clinical pathological features of patients with ESCC. MS-275 markedly reduced HDAC1 and HDAC2 expression, whereas increased the level of AcH3 and AcH2B. MS-275 suppressed proliferation and clonogenicity of ESCC cells in a concentration-dependent manner. In addition, MS-275 induced apoptosis, arrested cell cycle, and inhibited migration, epithelial–mesenchymal transition, and sphere-forming ability of ESCC cells in vitro. Moreover, p-Akt1 and p-mTOR were downregulated by MS-275. Finally, MS-275 significantly inhibited tumor growth in vivo. Taken together, HDAC1 and HDAC2 are associated with the progression of ESCC, and MS-275 hinders the progression and stemness of ESCC cells by suppressing the PI3K/Akt/mTOR pathway. Our findings show that MS-275 inhibits ESCC cells growth in vitro and in vivo, which is a potential drug for the ESCC therapy.

Original languageEnglish (US)
Pages (from-to)22400-22410
Number of pages11
JournalJournal of Cellular Physiology
Volume234
Issue number12
DOIs
StatePublished - Jan 1 2019

Keywords

  • MS-275
  • PI3K/Akt/mTOR
  • cancer stemness
  • esophageal squamous cell carcinoma
  • progression

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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    Ma, S., Liu, T., Xu, L., Wang, Y., Zhou, J., Huang, T., Li, P., Liu, H., Zhang, Y., Zhou, X., Cui, Y., Zang, X., Wang, Y., & Guan, F. (2019). Histone deacetylases inhibitor MS-275 suppresses human esophageal squamous cell carcinoma cell growth and progression via the PI3K/Akt/mTOR pathway. Journal of Cellular Physiology, 234(12), 22400-22410. https://doi.org/10.1002/jcp.28805