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
  • 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. [email protected].
  • 6. China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. [email protected].
  • 7. The Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, 450008, Henan, China. [email protected].
  • 8. The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, 450008, Henan, China. [email protected].
  • 9. International joint research center of cancer chemoprevention, Zhengzhou, China. [email protected].
  • 10. The Pathophysiology Department, The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450008, Henan, China. [email protected].
  • 11. China-US (Henan) Hormel Cancer Institute, Zhengzhou, 450008, Henan, China. [email protected].
  • 12. The Collaborative Innovation Center of Henan Province for Cancer Chemoprevention, Zhengzhou, 450008, Henan, China. [email protected].
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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