Silencing CDH17 reverses cisplatin resistance in gastric cancer cells by regulating the Warburg effect mediated by the Wnt/β-catenin pathway.

[OBJECTIVE] To investigate the role of CDH17 in cisplatin (DDP) resistance in gastric cancer (GC) and to elucidate the potential molecular mechanisms.

[METHODS] DDP-resistant GC cell lines were established, and CDH17 expression was silenced in these cells. Cell proliferation was assessed using the MTT assay. Cellular glycolytic activity was quantified, and apoptosis was assessed using flow cytometry. The expression of CDH17, β-catenin, key Warburg-related effector proteins, and Cleaved-caspase-3 was determined through molecular experiments. The Warburg effect inhibitor 2-DG and the Wnt/β-catenin signaling pathway agonist CP21R7 were applied to investigate the underlying molecular mechanism.

[RESULTS] CDH17 was significantly upregulated in the DDP-resistant GC cells. CDH17 knockdown increased the sensitivity of GC cells to DDP, suppressed the Warburg effect, and inhibited the activation of the Wnt/β-catenin signaling pathway. Treatment with 2-DG reduced the chemoresistance in resistant GC cells. However, CP21R7 treatment promoted the Warburg effect in the DDP-resistant GC cells and partially attenuated the effects of CDH17 silencing on both the Warburg effect and DDP sensitivity.

[CONCLUSION] CDH17 silencing reversed DDP resistance in GC cells, primarily through inhibition of the Warburg effect mediated by the Wnt/β-catenin signaling pathway.