Abstract: Background and purpose: EPHA2 has been reported to enhance the proliferation of gastric cancer cells through promoting CyclinD1 expression and cell cycle progression. However, the underlying mechanism that EPHA2 promotes CyclinD1 expression and cell cycle progression is still poorly understood. Akt/mTOR signaling pathway has been reported to enhance the proliferation of gastric cancer cells by promoting CyclinD1 expression and cell cycle progression, and some studies have shown that EPHA2 can activate Akt/mTOR signaling pathway. Based on this, this study investigated whether EPHA2 promoted gastric cancer SGC-7901 cell proliferation through enhancing Akt/mTOR signaling pathway. Methods: Western blot was used to determine the effect of EPHA2 overexpression or knockdown on the phosphorylation of Akt and mTOR in SGC-7901 cells. SGC-7901-NC infected with control lentivirus and SGC-7901-EPHA2 cells with EPHA2 overexpression were treated with DMSO, MK2206 (an Akt inhibitor) and RAD001 (a mTOR inhibitor) for different time periods, respectively. Cell proliferation was detected using the CCK8 assay. Cell cycle was detected using flow cytometry, and the expression of CyclinD1 was determined by Western blot. Results: Overexpression of EPHA2 enhanced Akt/mTOR signaling pathway in SGC-7901 cells, and silencing EPHA2 in SGC-7901 cells inhibited Akt/mTOR signaling pathway. MK2206 and RAD001 antagonized the promoting effect of EPHA2 on the proliferation, S-phase and CyclinD1 expression of SGC-7901 cells, respectively. Conclusion: EPHA2 promotes SGC-7901 cell proliferation through enhancing Akt/mTOR signaling pathway. Akt inhibitor or mTOR inhibi-tor could be an effective treatment strategy for gastric cancer patients overexpressing EPHA2.

Key words: EPHA2, Akt/mTOR signaling pathway, Gastric cancer, SGC-7901 cell