ABSTRACT

Overexpression of eukaryotic initiation factor- 5A2 (eIF5A2) has been implicated in promoting tumor cell migration and invasion in many cancers. However, whether eIF5A2 could be as the target for prostate cancer (PCa) treatment is still unknown. In this study, small interfering RNA specific for eIF5A2 (eIF5A2 siRNA) and lentivector for eIF5A2 shRNA (Lv-eIF5A2 shRNA) was performed to down-regulate eIF5A2 expression in PCa PC-3 M IE8 cells and in animal tumor model, respectively. The biological function of eIF5A2 siRNA or Lv-eIF5A2 shRNA on PC-3 M IE8 cell growth, apoptosis, migration, invasion and lung metastasis were explored. The results showed that targeting eIF5A2 inhibited PC-3 M IE8 cell invasion, migration, proliferation and increased cell apoptosis in vitro, and inhibited tumor growth and lung metastasis in vivo. Analysis of eIF5A2 signaling pathways in the clonal derivatives showed a decrease in MMP-2 and MMP-9 activation and increase in bcl-2 expression. We therefore concluded that therapies targeting the eIF5A2 signaling pathway may be more effective to prevent organ metastasis and primary tumor formation.

摘要

真核起始因子-5A2 (eIF5A2) 的过度表达与促进许多癌症中的肿瘤细胞迁移和侵袭有关。然而，eIF5A2 是否可以作为前列腺癌 (PCa) 治疗的靶点仍然未知。在本研究中，对 eIF5A2 特异的小干扰 RNA (eIF5A2 siRNA) 和针对 eIF5A2 shRNA 的慢病毒载体 (Lv-eIF5A2 shRNA) 分别用于下调 PCa PC-3 M IE8 细胞和动物肿瘤模型中的 eIF5A2 表达。探讨了eIF5A2 siRNA或Lv-eIF5A2 shRNA对PC-3 M IE8细胞生长、凋亡、迁移、侵袭和肺转移的生物学功能。结果表明靶向eIF5A2在体外抑制PC-3 M IE8细胞侵袭、迁移、增殖并增加细胞凋亡，并在体内抑制肿瘤生长和肺转移。对克隆衍生物中 eIF5A2 信号通路的分析表明，MMP-2 和 MMP-9 激活减少，bcl-2 表达增加。因此，我们得出结论，针对 eIF5A2 信号通路的疗法可能更有效地预防器官转移和原发性肿瘤的形成。