Conclusion
</strong> These findings suggested that the inhibition of PHGDH promoted cisplatin resistance in gastric cancer<br />through various intercellular mechanisms. And appropriate serine supplementation or the modulation of EP300 and<br />HSPA8 may be of great help in overcoming cisplatin resistance in gastric cancer.
Results
</strong> The inhibition of PHGDH significantly increased the viability and decreased the apoptotic rate induced by cisplatin<br />in gastric cancer cells. mRNA-Seq analysis revealed that the combined treatment of NCT503 reduced the number of DEGs<br />induced by cisplatin. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment<br />Analysis (GSEA) showed that unfolded protein response, ECM receptor interaction and cell cycle signaling pathways were<br />modulated by NCT503 treatment. Hub genes were identified by using protein-protein interaction network modeling, of which E1A binding protein p300 (EP300) and heat shock protein family A (Hsp70) member 8 (HSPA8) act as the vital genes in cisplatin resistance induced by the inhibition of PHGDH.<br /><strong>