2. Academic Validation
  3. 2,6-DMBQ is a novel mTOR inhibitor that reduces gastric cancer growth in vitro and in vivo

2,6-DMBQ is a novel mTOR inhibitor that reduces gastric cancer growth in vitro and in vivo

  • J Exp Clin Cancer Res. 2020 Jun 9;39(1):107. doi: 10.1186/s13046-020-01608-9.
Xueyin Zu 1 2,  Xiaoli Ma 1 2,  Xiaomeng Xie 1 2,  Bingbing Lu 1 2,  Kyle Laster 2,  Kangdong Liu 1 2 3 4,  Zigang Dong 5 6 7 8 9,  Dong Joon Kim 10 11 12
Affiliations

Affiliations

  • 1 The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450008, Henan, China.
  • 2 China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China.
  • 3 The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, 450008, Henan, China.
  • 4 The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, 450008, Henan, China.
  • 5 The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450008, Henan, China. zgdong@hci-cn.org.
  • 6 China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. zgdong@hci-cn.org.
  • 7 The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, 450008, Henan, China. zgdong@hci-cn.org.
  • 8 The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, 450008, Henan, China. zgdong@hci-cn.org.
  • 9 International joint research center of cancer chemoprevention, Zhengzhou, China. zgdong@hci-cn.org.
  • 10 The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450008, Henan, China. djkim@hci-cn.org.
  • 11 China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. djkim@hci-cn.org.
  • 12 The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, 450008, Henan, China. djkim@hci-cn.org.
PMID: 32517736 DOI: 10.1186/s13046-020-01608-9
Abstract

Background: Fermented wheat germ extract has been reported to exert various pharmacological activities, including anti-oxidant, anti-cell growth and cell Apoptosis in various Cancer cells. Although 2,6-dimethoxy-1,4-benzoquinone (2,6-DMBQ) is a benzoquinone compound and found in fermented wheat germ extract, its Anticancer effects and molecular mechanism(s) against gastric Cancer have not been investigated.

Methods: Anticancer effects of 2,6-DMBQ were determined by MTT, soft agar, cell cycle and Annexin V analysis. Potential candidate proteins were screened via in vitro kinase assay and Western blotting. mTOR knockdown cell lines were established by lentiviral Infection with shmTOR. The effect of 2,6-DMBQ on tumor growth was assessed using gastric Cancer patient-derived xenograft models.

Results: 2,6-DMBQ significantly reduced cell growth and induced G1 phase cell cycle arrest and Apoptosis in gastric Cancer cells. 2,6-DMBQ reduced the activity of mTOR in vitro. The inhibition of cell growth by 2,6-DMBQ is dependent upon the expression of the mTOR protein. Remarkably, 2,6-DMBQ strongly reduced patient-derived xenograft gastric tumor growth in an in vivo mouse model.

Conclusions: 2,6-DMBQ is an mTOR Inhibitor that can be useful for treating gastric Cancer. It has therapeutic implications for gastric Cancer patients.

Keywords

2,6-DMBQ; Gastric cancer; Patient-derived xenograft; mTOR; p70S6K.

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