Inactivation of EGFR/AKT signaling enhances TSA-induced ovarian cancer cell differentiation
Inactivation of EGFR/AKT signaling enhances TSA-induced ovarian cancer cell differentiation
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EGFR/AKT 信号失活增强 TSA 诱导的卵巢癌细胞分化
DOI：
10.3892/or.2017.5556
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发表时间：
2017-05-01
期刊：
影响因子：
4.2
通讯作者：
Zou, Shengqiang
中科院分区：
文献类型：
--
作者：
Shao, Genbao;Lai, Wensheng;Zou, Shengqiang
卵巢肿瘤是最致命的妇科肿瘤之一，但其分化治疗的特点较差。在这里，我们证明了众所周知的组蛋白脱乙酰酶(HDACs)抑制剂--苏维菌素A(TSA)可以诱导HO8910卵巢癌细胞分化。TSA诱导的细胞分化具有典型的形态改变，分化标记FOXA2表达增加，多能标记SOX2和OCT4表达降低，抑制细胞增殖，细胞周期停滞于G(1)期。TSA还可诱导细胞周期抑制蛋白p21(Cipl)表达增加，细胞周期调节蛋白cyClinD1表达降低。值得注意的是，用表皮生长因子受体(EGFR)信号通路的特异性抑制剂阻断该信号通路可促进TSA诱导的HO8910细胞分化。这些结果表明，EGFR级联抑制剂联合TSA可能是一种有前途的卵巢癌分化治疗策略。
Ovarian tumor is one of the most lethal gynecologic cancers, but differentiation therapy for this cancer is poorly characterized. Here, we show that thrichostatin A (TSA), the well known inhibitor of histone deacetylases (HDACs), can induce cell differentiation in HO8910 ovarian cancer cells. TSA-induced cell differentiation is characterized by typical morphological change, increased expression of the differentiation marker FOXA2, decreased expression of the pluripotency markers SOX2 and OCT4, suppressing cell proliferation, and cell cycle arrest in the G(1) phase. TSA also induces an elevated expression of cell cycle inhibitory protein p21(Cipl) along with a decrease in cell cycle regulatory protein cyclin D1. Significantly, blockage of epidermal growth factor receptor (EGFR) signaling pathway with specific inhibitors of this signaling cascade promotes the TSA-induced differentiation of HO8910 cells. These results imply that the EGFR cascade inhibitors in combination with TSA may represent a promising differentiation therapy strategy for ovarian cancer.