Dezocine regulates the malignant potential and aerobic glycolysis of liver cancer targeting Akt1/GSK-3β pathway

Zi-Wen Zhong; Wen-Chang Zhou; Xing-Feng Sun; Qi-Chao Wu; Wan-Kun Chen; Chang-Hong Miao

doi:10.21037/atm.2020.03.28

Dezocine regulates the malignant potential and aerobic glycolysis of liver cancer targeting Akt1/GSK-3β pathway

Ann Transl Med. 2020 Apr;8(7):480. doi: 10.21037/atm.2020.03.28.

Authors

Zi-Wen Zhong^{1

2

3}, Wen-Chang Zhou^{1

2

3}, Xing-Feng Sun^{1

2

3}, Qi-Chao Wu^{1

2

3}, Wan-Kun Chen^{1

2

3}, Chang-Hong Miao^{1

2

3}

Affiliations

¹ Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
² Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
³ Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Abstract

Background: Due to the "ceiling effect" of respiratory depression and the non-addictiveness, the consumption of dezocine is increasing quickly in the cancer surgery perioperative period for security and comfort reasons in China. Former studies find dezocine inhibits the norepinephrine transporters (NET) and serotonin transporters (SERT) and sigma-1opioid receptors. Given the complexity of the molecular mechanism, the effect of dezocine on tumor cells need to be studied. In this study, we investigated the effect of dezocine on HepG2 and Hep 3B liver cancer cell lines growth and glycolysis, and the molecular mechanisms behind.

Methods: HepG2 and Hep 3B cells viability and migration were measured by CCK8, Wound healing and transwell assay, Extracellular acidification rate (ECAR) was used to index the aerobic glycolysis of liver cancer cells and western blot analysis showed protein expression levels in the cells. SC79, an agonist of Akt, and the siRNA silence of Akt1 aimed to regulate Akt1 activity and expression in the reverse experiments.

Results: Dezocine played opposite roles in HepG2 and Hep 3B cells viability and migration in a concentration-dependent manner (P<0.01). Dezocine has diverse effects on aerobic glycolysis and adjusts the serine/threonine kinase 1 (Akt1)-glycogen synthase kinase-3β (GSK-3β) pathway. The effects of SC79 and the siRNA silence of Akt1 could reverse the effects of dezocine on HepG2 and Hep 3B cells.

Conclusions: As an analgesic drug widely used in clinical practice, dezocine play reversed roles on HepG2 and Hep 3B cells viability and migration targeting Akt1/GSK-3β pathway then the glycolysis in a concentration-dependent manner.

Keywords: Dezocine; glycolysis; liver cancer.