Bufalin reverses oxaliplatin resistance in gastric cancer by targeting YBX1 to suppress glycolysis

  • Biochem Pharmacol. 2026 Aug;250(Pt 1):117976. doi: 10.1016/j.bcp.2026.117976.
Xiaotong Li  1 ,  Qiuying Li  2 ,  Zhenhua Ni  3 ,  Zengyou Xiao  4 ,  Zean Yang  4 ,  Qingsong Zuo  1 ,  Wei Li  1 ,  Xiongbiao Wang  5 ,  Teng Chen  6 ,  Jie Wang  7
Affiliations
  • 1. Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 200063 Shanghai, China.
  • 2. Department of Interventional Pain Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 200063 Shanghai, China.
  • 3. Department of Experimental Medicine Centre, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 200063 Shanghai, China.
  • 4. Department of General Surgery, Shanghai Putuo Central School of Clinical Medicine, Anhui Medical University, 200063 Shanghai, China.
  • 5. Department of Pulmonology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 200063 Shanghai, China. Electronic address: [email protected].
  • 6. Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 200063 Shanghai, China. Electronic address: [email protected].
  • 7. Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 200063 Shanghai, China; Department of General Surgery, Shanghai Putuo Central School of Clinical Medicine, Anhui Medical University, 200063 Shanghai, China. Electronic address: [email protected].
PMID: 41991006 DOI: 10.1016/j.bcp.2026.117976
Abstract

Oxaliplatin resistance is a key challenge in gastric Cancer therapy. This study explored how bufalin, an active component of Chansu, reverses this resistance. We found that bufalin targets the transcription factor YBX1, which is upregulated in resistant cells. YBX1 activates STC1 expression, leading to PI3K/Akt pathway activation, increased HK2 levels, and enhanced glycolysis-all contributing to resistance. Bufalin inhibits this YBX1/STC1/glycolysis axis. Using in vitro assays (proliferation, Apoptosis, glycolysis measurement) and in vivo models, we demonstrated that bufalin suppresses glycolysis and restores oxaliplatin sensitivity. Mechanistic studies (RNA-seq, ChIP, SPR, etc.) confirmed the direct YBX1-bufalin interaction. Our work reveals YBX1/STC1-mediated glycolysis as a novel resistance mechanism and identifies bufalin as a promising therapeutic agent to overcome it.

Keywords
Bufalin; Chemoresistance; Gastric cancer; Glycolysis; STC1; YBX1.
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