2. Academic Validation
  3. Ginsenoside Rh4 suppresses aerobic glycolysis and the expression of PD-L1 via targeting AKT in esophageal cancer

Ginsenoside Rh4 suppresses aerobic glycolysis and the expression of PD-L1 via targeting AKT in esophageal cancer

  • Biochem Pharmacol. 2020 Aug;178:114038. doi: 10.1016/j.bcp.2020.114038.
Xuqian Deng 1,  Jiaqi Zhao 2,  Linlin Qu 1,  Zhiguang Duan 1,  Rongzhan Fu 1,  Chenhui Zhu 3,  Daidi Fan 4
Affiliations

Affiliations

  • 1 Shaanxi Key Laboratory of Degradable Biomedical Materials and Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China; Biotech & Biomed Research Institute, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China.
  • 2 School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 3 Shaanxi Key Laboratory of Degradable Biomedical Materials and Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China; Biotech & Biomed Research Institute, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China. Electronic address: zch2005@nwu.edu.cn.
  • 4 Shaanxi Key Laboratory of Degradable Biomedical Materials and Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China; Biotech & Biomed Research Institute, Northwest University, Taibai North Road 229, Xi'an, Shaanxi 710069, China. Electronic address: fandaidi@nwu.edu.cn.
PMID: 32422139 DOI: 10.1016/j.bcp.2020.114038
Abstract

Ginsenoside Rh4, as a bioactive component obtained from Panax notoginseng, has excellent pharmacological efficacy especially antitumor effects. However, its Anticancer effects and target mechanisms in regulating human esophageal Cancer are still poorly understood. Here, the results suggested that Rh4 exhibited potent anti-esophageal Cancer effects in vivo and in vitro. Flow cytometric analysis and Western Blot showed that Rh4 significantly inhibited the growth by inducing G1 phase arrest. In parallel, Rh4 inhibited aerobic glycolysis in esophageal Cancer cells by hindering lactate production, glucose uptake and ATP production; reducing the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR); suppressing aerobic glycolysis-related protein expression. Mechanistic studies demonstrated that Akt is a possible target of Rh4, which suppresses aerobic glycolysis. Rh4 administration resulted in Akt deregulation, whereas treatment with Insulin abolished the inhibitory effect of Rh4 on aerobic glycolysis. In contrast, treatment with Akt inhibitors or siRNA that silenced Akt enhanced the inhibitory effect of Rh4 on aerobic glycolysis. Moreover, molecular docking results indicated that Rh4 was able to bind to the interdomain region of Akt. Interestingly, the results revealed that Rh4 also inhibited the expression of PD-L1 via the Akt/mTOR pathway. Taken together, our findings provide important insights into the anti-esophageal Cancer effects of Rh4 via suppressing aerobic glycolysis and PD-L1 expression, which indicated Rh4 could be as promising drug for clinical treatment.

Keywords

AKT; Aerobic glycolysis; Esophageal cancer; Ginsenoside Rh4; PD-L1.

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