2. Academic Validation
  3. Inhibition of AMPK/PFKFB3 mediated glycolysis synergizes with penfluridol to suppress gallbladder cancer growth

Inhibition of AMPK/PFKFB3 mediated glycolysis synergizes with penfluridol to suppress gallbladder cancer growth

  • Cell Commun Signal. 2022 Jul 16;20(1):105. doi: 10.1186/s12964-022-00882-8.
Jiahao Hu  # 1 2,  Jiasheng Cao  # 1 2,  Ren'an Jin  # 1,  Bin Zhang 1 2,  Win Topatana 1 2,  Sarun Juengpanich 1 2,  Shijie Li 1 2,  Tian'en Chen 1 2,  Ziyi Lu 2,  Xiujun Cai 3 4 5 6 7,  Mingyu Chen 8 9
Affiliations

Affiliations

  • 1 Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, No. 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China.
  • 2 School of Medicine, Zhejiang University, Hangzhou, 310058, Zhejiang Provinc, China.
  • 3 Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, No. 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. srrsh_cxj@zju.edu.cn.
  • 4 School of Medicine, Zhejiang University, Hangzhou, 310058, Zhejiang Provinc, China. srrsh_cxj@zju.edu.cn.
  • 5 Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, No. 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. srrsh_cxj@zju.edu.cn.
  • 6 Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease, Hangzhou, China. srrsh_cxj@zju.edu.cn.
  • 7 Zhejiang Research and Development Engineering Laboratory of Minimally Invasive Technology and Equipment, Hangzhou, China. srrsh_cxj@zju.edu.cn.
  • 8 Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, No. 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. mychen@zju.edu.cn.
  • 9 Key Laboratory of Laparoscopic Technique Research of Zhejiang Province, No. 3 East Qingchun Road, Hangzhou, 310016, Zhejiang Province, China. mychen@zju.edu.cn.
  • # Contributed equally.
PMID: 35842652 DOI: 10.1186/s12964-022-00882-8
Abstract

Background: Penfluridol (PF) is an FDA-approved antipsychotic drug that has recently been shown to have Anticancer activity. However, the Anticancer effects and underlying mechanisms of PF are not well-established in gallbladder Cancer (GBC).

Methods: The Anticancer efficacy of PF on GBC was investigated via a series of cell functions experiments, including cell viability, colony formation, Apoptosis assays, and so on. The corresponding signaling changes after PF treatment were explored by western blotting. Then, nude mice were utilized to study and test the Anticancer activity of PF in vivo. Besides, glucose consumption and lactic production assays were used to detect the glycolysis alteration.

Results: In this study, we discovered that PF greatly inhibited the proliferation and invasion ability of GBC cells (GBCs). The glucose consumption and lactic generation ability of GBCs were dramatically elevated following PF treatment. Additionally, we discovered that inhibiting glycolysis could improve PF's Anticancer efficacy. Further studies established that the activation of the AMPK/PFKFB3 signaling pathway medicated glycolysis after PF treatment. We proved mechanistically that inhibition of AMPK/PFKFB3 singling pathway mediated glycolysis was a potential synergetic strategy to improve the Anticancer efficacy of PF on GBC.

Conclusions: By inhibiting AMPK, the Anticancer effects of PF on GBCs were amplified. As a result, our investigations shed new LIGHT on the possibility of repurposing PF as an Anticancer drug for GBC, and AMPK inhibition in combination with PF may represent a novel therapeutic strategy for GBC. Video abstract.

Keywords

AMPK/PFKFB3; Apoptosis; Gallbladder cancer; Glycolysis; Penfluridol.

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