真核起始因子4A1在胃癌中的表达及其在胃癌细胞增殖、侵袭及迁移中的作用

Expression of eukaryotic initiation factor 4A1 in gastric cancer and its role in proliferation, invasion and migration of gastric cancer cells

目的:探讨真核起始因子4A1(eIF4A1)在胃癌中的表达及其在胃癌细胞增殖、侵袭及迁移中的作用。方法:收集116对胃癌组织及相应的癌旁正常组织,用免疫组化、RT-PCR及Western blot检测eIF4A1的表达;用MTT法检测不同浓度的eIF4A1抑制剂hippuristanol(0.125、0.25、0.5、1、2 μmol/L)对胃癌细胞株AGS、MGC-803及正常胃黏膜细胞GES-1增殖的影响;Transwell及划痕实验检测hippuristanol对胃癌细胞株的侵袭和迁移能力的影响。结果:免疫组化结果显示,eIF4A1在胃癌组织中的表达明显高于癌旁正常组织(P<0.05),RT-PCR及Western blot验证结果与免疫组化结果一致。MTT结果显示,hippuristanol呈浓度与时间依赖性抑制胃癌细胞株AGS、MGC-803的增殖,而达0.5 μmol/L以上时才对正常胃黏膜细胞GES-1的增殖有抑制作用(均P<0.05);用0.125 μmol/L的hippuristanol处理的AGS、MGC-803细胞24 h后,两种细胞的侵袭能力及迁移能力均明显下降(均P<0.05)。结论:eIF4A1在胃癌中呈高表达,且与胃癌细胞的恶性特征密切相关,eIF4A1抑制剂有望成为治疗胃癌的候选药物。

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.