IL-8调节卵巢癌细胞VEGF表达、体外黏附与侵袭特性的机制研究

The mechanisms of IL-8 in regulating VEGF expression level,cell adhesion and invasion of ovarian cancer cells in vitro

目的探讨IL-8对卵巢癌细胞VEGF表达水平、体外黏附和侵袭特性的影响及相关分子机制。方法在原工作基础上,利用前期构建的过表达IL-8的人卵巢癌A2780细胞株和抑制表达IL-8的人卵巢癌SKOV3细胞株,分别应用半定量RT-PCR法、Western blot技术、细胞体外黏附实验、Transwell小室体外侵袭实验及明胶酶谱法等观察IL-8对卵巢癌细胞VEGF表达、黏附和侵袭特性的影响,并对其作用机制和可能的信号通路进行研究。结果与对照组相比,过表达IL-8可增强卵巢癌细胞VEGF的基因转录和蛋白表达水平,促进细胞的体外黏附和侵袭能力(P<0.001);抑制IL-8表达,细胞的VEGF表达水平和黏附、侵袭能力均减弱。进一步研究发现,IL-8的促细胞黏附和侵袭活性,与激活PI3K/Akt和Raf/MEK/ERK信号通路、增强MMP-2和MMP-9的活性和表达水平密切相关。结论 IL-8可促进卵巢癌细胞VEGF表达,增强细胞的黏附侵袭能力;IL-8及其相关信号分子有望成为抑制肿瘤转移、延缓病程进展的新靶点。

This study designed to explore the mechanisms of interleukin-8 （IL-8） in regulating VEGF expression, cell adhesion and invasion of ovarian cancer （OVCA） cells and its related signal pathways. Based on our previous studies, overexpression of IL-8 in non-IL-8-expressing A2780 cells （by transfecting with plasmid encoding for sense IL-8） increases VEGF level, cell adhesion and invasion in vitro, while depletion of IL-8 in IL- 8-overexpressing SKOV3 cells （by transfecting with plasmid encoding for antisense IL-8） decreases the above effects. Further investigation indicated that IL-8-stimulated cell adhesion correlated with aetivation of PI3K/Akt and Raf/MEK/ERK, whereas IL-8-enhanced OVCA cell invasive correlated with increased MMP-2 and MMP-9 activity and expression. These data suggest that IL-8 secreted by OVCA cells can promote angiogenic potential, cell adhesion and invasion. Therefore, modulation of IL-8 expression or its related signaling pathway may be a promising strategy for controlling the progression and metastasis of OVCA.