胰岛素样生长因子-II对卵巢癌细胞AO、3AO中MMP-2表达的调节

Insulin-like growth factor-II modulates secretions of matrix metalloproteinase-2 in epithelial ovarian cancer cell lines AO and 3AO

目的:探讨胰岛素样生长因子鄄II(insulin鄄likegrowthfactor鄄II,IGF鄄II)对卵巢癌细胞AO、3AO基质金属蛋白酶鄄2(matrixmetalloproteinase鄄2,MMP鄄2)表达的诱导调节。方法:以IGF鄄II处理卵巢癌细胞AO、3AO,用明胶酶谱法和RT鄄PCR法检测MMP鄄2蛋白的分泌以及基因表达。结果:IGF鄄II能双相调节浆液性囊腺癌细胞AO中MMP鄄2的分泌,低浓度(10ng/ml)时能上调MMP鄄2的分泌,随着IGF鄄II的浓度增加该作用增强;但高浓度时(100ng/ml),诱导作用显著下降;IGF鄄II不增加粘液性囊腺癌细胞3AO培养上清中MMP鄄2蛋白的分泌。此外,IGF鄄II不影响两种卵巢癌细胞中MMP鄄2的基因表达。结论:IGF鄄II在一定程度上能刺激上皮性卵巢癌MMP鄄2蛋白表达,可能在卵巢癌的侵袭转移方面起重要作用。

Objective: To investigate the effect of insulin-like growth factor-II(IGF-II) on matrix metalloproteinase-2(MMP-2) expression in ovarian cancer cell lines AO and 3AO. Methods: Cells with a density of 1.5×105/ml were cultured for 48 hours and then treated with IGF-II at different concentrations for additional 18 hours. MMP-2 secretion in conditional medium was analyzed by gelatin zymography and MMP-2 mRNA was measured by RT-PCR. Results: The analysis of gelatin zymography showed that the secretion of MMP-2 in AO increased with the increase of IGF-II. With the treatment of higher concentration(100 ng/ml) of IGF-II,MMP-2 had a significantly decreased concentration. However, MMP-2 level in the supernatant after treatment was not different from that of the control group in 3AO. The expression of MMP-2 mRNA in AO and 3AO had no response to IGF-II stimulation. Conclusion: IGF-II may play an important role in invasion and metastasis of ovarian cancer through increasing of MMP-2 protein secretion.