Activation of the PI3K/AKT pathway mediates FSH-stimulated VEGF expression in ovarian serous cystadenocarclnoma

有证据建议那刺激滤泡的荷尔蒙(FSH ) 能由在癌症细胞增加脉管的 endothelial 生长因素(VEGF ) 表示便于卵巢的癌症的 neovascularization，尽管这个过程的内在的分子的机制不是众所周知的。因此，我们在卵巢的癌症房间线 SKOV-3 和 ES-2 在 VEGF 表示上调查了 FSH 的效果。有 FSH 的治疗显著地在一个剂量依赖者和时间依赖者举止增加了 VEGF 表示。另外， FSH 治疗提高了 survivin 和组织缺氧可诱导的 factor-1 (HIF-1 ) 的表示。survivin 或 HIF-1 击倒压制的 VEGF 表示，但是 survivin 仅仅击倒禁止的刺激 FSH 的 VEGF 表示。有 LY294002 的预告的处理，一个 phosphoinositide 3-kinase (PI3K )/AKT 禁止者，抵销 FSH，而是治疗与 U0126 导致的 survivin 的提高的表示，激活 mitogen 的蛋白质 kinase/extracellular 调整信号的 kinase 禁止者，没有如此的效果。我们进一步证明卵巢的浆液的 cystadenocarcinoma 样品有积极 AKT 和比的染色的 phosphorylated AKT (pAKT ) 蛋白质的许多更高的发生良性的卵巢的 cystadenoma 取样了(p < 0.01 ) 。5 年的幸存率仅仅在有卵巢的浆液的 cystadenocarcinoma 的病人是大约 15% 有 AKT 和 pAKT 表示，而它在没有 AKT 或 pAKT 表示的那些是大约 80% 。一起拿，这些结果显示 FSH 由 upregulating 增加 VEGF 的表示 survivin 的表示，它被发信号的 PI3K/AKT 激活小径。在 survivin 和 VEGF 的刺激 FSH 的表示理解 PI3K/AKT 小径的角色将为与卵巢的浆液的 cystadenocarcinoma 为病人评估预后并且为对这疾病追求有效治疗是有益的。

There is evidence to suggest that follicle-stimulating hormone （FSH） can facilitate the neovascularization of ovarian cancers by increasing vascular endothelial growth factor （VEGF） expression in cancer cells, although the underlying molecular mechanism of this process is not well known. Therefore, we investigated the effect of FSH on VEGF expression in the ovarian cancer cell lines SKOV-3 and ES-2. Treatment with FSH significantly increased VEGF expression in a dose- and time-dependent manner. In addition, FSH treatment enhanced the expression of survivin and hypoxlainducible factor-1 （HIF-1α）. Knockdown of survivin or HIF-1α suppressed VEGF expression, but only knockdown of survivin inhibited FSH-stimulated VEGF expression. Pretreatment with LY294002, a phosphoinositide 3-kinase （PI3K）/AKT inhibitor, neutralized the enhanced expression of survivin induced by FSH, but treatment with U0126, a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor, had no such effect. We further showed that ovarian serous cystadenocarcinoma samples had much higher incidence of positive AKT and phosphorylated AKT （pAKT） protein staining than did benign ovarian cystadenoma samples （p 〈 0.01）. The 5-year survival rate was only about 15% in patients with ovarian serous cystadenocarcinoma who had AKT and pAKT expression, whereas it was about 80% in those who did not have AKT or pAKT expression. Taken together, these results indicate that FSH increases the expression of VEGF by upregulating the expression of survivin, which is activated by the PI3K/AKT signaling pathway. Understanding the role of the PI3K/AKT pathway in FSH-stimulated expression of survivin and VEGF will be beneficial for evaluating the prognosis for patients with ovarian serous cystadenocarcinoma and for pursulug effective treatment against this disease.