Abstract: Objective · To investigate the role and mechanism of glutamic-pyruvic transaminase 2 (GPT2) on cisplatin resistance in gastric cancer. Methods · The Kaplan Meier-Plotter database was used to analyze the relationship between GPT2 and poor prognosis of gastric cancer. The s of GPT2 in gastric cancer cells and tissues were detectedquantitative real-time PCR (qPCR), Western blotting and immunohistochemistry (IHC). The cytotoxicity of cisplatin at different concentrations to human gastric cancer cells and normal gastric epithelial cells was detectedCCK-8 assay. GPT2 over and knockdown cell lines were constructed in cisplatin sensitive MKN28 cells and insensitive MKN45 cells, respectively. CCK-8 assay, colony formation assay and Western blotting were performed to evaluate the cellular cytotoxicity, stemness of cancer cells and the changes of key proteins in stemness-related signaling pathways in GPT2 over and knockdown cell lines, respectively. Results · The high of GPT2 was negatively correlated with the survival of gastric cancer patients. Gastric cancer cells with high of GPT2 were resistant to cisplatin, while cells with low of GPT2 were sensitive to cisplatin. Over of GPT2 could decrease the cell sensitivity to cisplatin, nevertheless knockdown of GPT2 could increase the cell sensitivity to cisplatin. Meanwhile, the further study revealed that over of GPT2 could activate the extracellular regulated protein kinases (ERK) signaling pathway, up-regulate the of SRY-box 2 (SOX2) and Nanog homeobox (NANOG), and enhance the ability of colony formation, while knockdown of GPT2 could inhibit ERK signaling pathway, reduce the of SOX2 and NANOG, and suppress the ability of colony formation. Conclusion · GPT2 are related to the sensitivity of cisplatin treatment. Over of GPT2 can increase the resistance of gastric cancer to cisplatin treatmentactivating ERK signaling pathway and up-regulating the of SOX2 and NANOG.

Key words: glutamic-pyruvic transaminase 2 (GPT2), gastric cancer, cisplatin, treatment resistance