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The inhibition of biological behavior of gastric cancer cells by penfluridol through HSP90/Akt/MDM2/p53 signaling pathway
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Pei-li WANG1, 2, Qi-feng CHEN1, 2, Yi-xuan HUO2, Jia-rui WANG5, Rong HE2, Li-he JIANG1, 2, 3, 4, *
Acta Pharmaceutica Sinica | 2025, 60(8) : 2528 - 2534
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Acta Pharmaceutica Sinica | 2025, 60(8): 2528-2534
• Original Articles •
The inhibition of biological behavior of gastric cancer cells by penfluridol through HSP90/Akt/MDM2/p53 signaling pathway
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Pei-li WANG1, 2, Qi-feng CHEN1, 2, Yi-xuan HUO2, Jia-rui WANG5, Rong HE2, Li-he JIANG1, 2, 3, 4, *
Affiliations
  • 1Medical School of Guangxi University, Nanning 530004, China
  • 2Basic Medical College of Youjiang Medical University for Nationalities, Baise 533000, China
  • 3Guangxi Key Laboratory for Pharmaceutical Molecular Discovery and Druggability Optimization, School of Pharmacy, Guilin Medical University, Guilin 541199, China
  • 4Guangxi Colleges and Universities Key Laboratory of Human Development and Disease Research (Guangxi Medical University), Nanning 530021, China
  • 5School of Medical Laboratory Science, Youjiang Medical University for Nationalities, Baise 533000, China
Published: 2025-08-12 doi: 10.16438/j.0513-4870.2025-0058
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This study investigated the antitumor activity and molecular mechanisms of penfluridol (PF), an antipsychotic drug, in gastric cancer treatment. In vitro assays including CCK-8, colony formation, wound healing, Transwell migration, Hoechst 33342 staining, and flow cytometry demonstrated that penfluridol significantly inhibited proliferation and migration of SGC-7901 and HGC-27 gastric cancer cells in a concentration-dependent manner, while inducing apoptosis. Transcriptomic profiling combined with molecular docking revealed stable binding conformations between penfluridol and heat shock protein 90 (HSP90) or mouse double minute 2 (MDM2). Western blot analysis further confirmed that penfluridol suppressed the HSP90/protein kinase B/MDM2/tumor protein p53 (HSP90/Akt/MDM2/p53) pathway, characterized by decreased HSP90 expression and concomitant upregulation of p53 protein. These findings collectively indicate that penfluridol exerts multifaceted antitumor effects by targeting key oncogenic pathways, providing experimental evidence for repurposing this antipsychotic agent as a potential therapeutic strategy against gastric cancer.

gastric cancer  /  drug repurposing  /  penfluridol  /  molecular docking  /  heat shock protein 90  /  transcriptomics
王珮郦, 陈奇峰, 霍艺萱, 王家瑞, 贺蓉, 蒋利和. 五氟利多通过HSP90/Akt/MDM2/p53信号通路抑制胃癌细胞生物学行为的研究. 药学学报, 2025 , 60 (8) : 2528 -2534 . DOI: 10.16438/j.0513-4870.2025-0058
Pei-li WANG, Qi-feng CHEN, Yi-xuan HUO, Jia-rui WANG, Rong HE, Li-he JIANG. The inhibition of biological behavior of gastric cancer cells by penfluridol through HSP90/Akt/MDM2/p53 signaling pathway[J]. Acta Pharmaceutica Sinica, 2025 , 60 (8) : 2528 -2534 . DOI: 10.16438/j.0513-4870.2025-0058
Appendix
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Year 2025 volume 60 Issue 8
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Article Info
doi: 10.16438/j.0513-4870.2025-0058
  • Receive Date：2025-01-16
  • Online Date：2026-09-20
  • Published：2025-08-12
Article Data
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History
  • Received：2025-01-16
  • Revised：2025-03-28
Affiliations
    1Medical School of Guangxi University, Nanning 530004, China
    2Basic Medical College of Youjiang Medical University for Nationalities, Baise 533000, China
    3Guangxi Key Laboratory for Pharmaceutical Molecular Discovery and Druggability Optimization, School of Pharmacy, Guilin Medical University, Guilin 541199, China
    4Guangxi Colleges and Universities Key Laboratory of Human Development and Disease Research (Guangxi Medical University), Nanning 530021, China
    5School of Medical Laboratory Science, Youjiang Medical University for Nationalities, Baise 533000, China
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小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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