Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Ganodermanontriol Suppresses the Progression of Lung Adenocarcinoma by Activating CES2 to Enhance the Metabolism of Mycophenolate Mofetil

  • Qingfeng Xie (Respiratory Department, Longquan People's Hospital) ;
  • Zhuo Cao (Respiratory Department, The Sixth Affiliated Hospital of Wenzhou Medical University) ;
  • Weiling You (Respiratory Department, Longquan People's Hospital) ;
  • Xiaoping Cai (Respiratory Department, The Sixth Affiliated Hospital of Wenzhou Medical University) ;
  • Mei Shen (Longquan People's Hospital) ;
  • Zhangyong Yin (Respiratory Department, The Sixth Affiliated Hospital of Wenzhou Medical University) ;
  • Yiwei Jiang (Wenzhou Medical University) ;
  • Xin Wang (Wenzhou Medical University) ;
  • Siyu Ye (School of Public Administration, Wenzhou Medical University)
  • Received : 2023.06.09
  • Accepted : 2023.09.20
  • Published : 2024.02.28
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Abstract

New anti-lung cancer therapies are urgently required to improve clinical outcomes. Since ganodermanontriol (GDNT) has been identified as a potential antineoplastic agent, its role in lung adenocarcinoma (LUAD) is investigated in this study. Concretely, lung cancer cells were treated with GDNT and/or mycophenolate mofetil (MMF), after which MTT assay, flow cytometry and Western blot were conducted. Following bioinformatics analysis, carboxylesterase 2 (CES2) was knocked down and rescue assays were carried out in vitro. Xenograft experiment was performed on mice, followed by drug administration, measurement of tumor growth and determination of CES2, IMPDH1 and IMPDH2 expressions. As a result, the viability of lung cancer cells was reduced by GDNT or MMF. GDNT enhanced the effects of MMF on suppressing viability, promoting apoptosis and inducing cell cycle arrest in lung cancer cells. GDNT up-regulated CES2 level, and strengthened the effects of MMF on down-regulating IMPDH1 and IMPDH2 levels in the cells. IMPDH1 and IMPDH2 were highly expressed in LUAD samples. CES2 was a potential target for GDNT. CES2 knockdown reversed the synergistic effect of GDNT and MMF against lung cancer in vitro. GDNT potentiated the role of MMF in inhibiting tumor growth and expressions of CES2 and IMPDH1/2 in lung cancer in vivo. Collectively, GDNT suppresses the progression of LUAD by activating CES2 to enhance the metabolism of MMF.

Keywords

Acknowledgement

This work was supported by the Zhejiang Provincial Medical and Health Project [2023587787]; the Zhejiang Provincial Science and Technology Department Project [LGF22H010012]; the Longquan Science and Technology Bureau Project [2021KJ-003]; the Zhejiang Provincial Medical and Health Research Project [2021KY1235]; the Lishui Science and Technology Bureau Project [2020077571].

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