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

• Main Authors: Xueyin Zu, Xiaoli Ma, Xiaomeng Xie, Bingbing Lu, Kyle Laster, Kangdong Liu, Zigang Dong, Dong Joon Kim
• Format: Article
• Language: English
• Published: BMC 2020-06-01
• Series: Journal of Experimental & Clinical Cancer Research
• Subjects: 2,6-DMBQ; mTOR; p70S6K; Gastric cancer; Patient-derived xenograft
• Online Access: http://link.springer.com/article/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.