Abstract:Objective: To investigate the expression of eukaryotic initiation factor 4A1 (eIF4A1) in gastric cancer and its role in the proliferation, invasion and migration of gastric cancer cells.
Methods: A total of 116 paired specimens of gastric cancer and their adjacent normal tissue were collected, and then, the expressions of eIF4A1 were analyzed by immunohistochemical staining, RT-RCR and Western blot. The effects of different concentrations of eIF4A1 inhibitor hippuristol (0.125, 0.25, 0.5, 1 and 2 μmol/L) on the proliferation of gastric cancer cell line AGS and MGC-803 as well as normal gastric mucosa cell line GES-1 were analyzed by MTT assay. The influences of hippuristol on invasion and migration abilities of the gastric cell lines were determined by Transwell assay and scratch assay.
Results: The results of immunohistochemical staining showed that the expression level of eIF4A1 in gastric cancer tissue was significantly higher than that in the adjacent normal tissue (P<0.05), and the results of RT-PCR and Western blot were consistent with the results of immunohistochemical staining. Results of MTT assay showed that the proliferative abilities in gastric cancer AGS and MGC-803 cells were significantly inhibited by hippuristanol in a time- and concentration-dependent manner, and not in the normal gastric mucosa GES-1 cells until the concentration of hippuristanol over 0.5 μmol/L (all P<0.05). In AGS and MGC-803 cells after exposure to 0.125 μmol/L hippuristanol for 24 h, the invasion and migration abilities were significantly reduced (both P<0.05).
Conclusion: The expression of eIF4A1 is increased in gastric cancer, which is closely associated with the malignant characteristics of gastric cancer cells. The eIF4A1 inhibitor may be expected to become a drug candidate for the treatment of gastric cancer.