eIF5A2 regulates the resistance of gastric cancer cells to cisplatin via induction of EMT.

Cisplatin is the first-line chemotherapy drug for gastric cancer (GC), but treatment failure often occurs due to development of resistance. The mechanism of cisplatin resistance remains a mystery. Eukaryotic translation initiation factor 5A2 (eIF5A2) is an important tumor-promoting factor and has been rarely studied in GC. This study aimed to investigate the role of eIF5A2 in cisplatin resistance of GC cells and its relationship with epithelial-mesenchymal transition (EMT). We found that it is negative correlation between cisplatin resistance and eIF5A2's expression in GC cells. Silencing of eIF5A2 enhanced the sensitivity of GC cells to cisplatin, while overexpression of eIF5A2 decreased sensitivity. Cisplatin treatment induced gene expression changes consistent with EMT. EMT was blocked and the sensitivity of GC cells to cisplatin was increased by inhibiting the expression of Twist, indicating that EMT regulates the sensitivity of GC cells to cisplatin. Knockdown of eIF5A2 was associated with upregulation of the epithelial markers E-cadherin and β-catenin, while the expression of mesenchymal markers vimentin and N-cadherin decreased, indicating that eIF5A2 can reverse the EMT process and block the effect of cisplatin on EMT-related markers. Knockdown or overexpression of eIF5A2 did not affect the sensitivity of gastric cancer cells to cisplatin by Twist siRNA. Altogether, these data suggest that eIF5A2 regulates the resistance of gastric cancer cells to cisplatin by mediating EMT, and support the conclusion that eIF5A2 may be a molecular target for anti-tumor therapy.