Molecular Medicine Reports, 2014, 9(5):1982-8.

FOXO3a-mediated suppression of the self-renewal capacity of sphere-forming cells derived from the ovarian cancer SKOV3 cell line by 7-difluoromethoxyl-5,4'-di-n-octyl genistein

Yingxia Ning, Chaoyuan Luo, Kaiqun Ren, et al

Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, P.R. China

Carcinogenesis is predominantly dependent on the cancer stem cells (CSCs) residing or populating within the cancer. We previously demonstrated that the novel synthetic genistein analogue, 7-difluoromethoxyl-5,4'-di-n-octylgenistein (DFOG), induced apoptotic cell death of ovarian and gastric cancer cells. The present study demonstrated that sphere‑forming cells (SFCs) derived from the ovarian cancer cell-line SKOV3 possessed ovarian cancer stem-like cell (OCSLC) properties, including self-renewal and high tumorigenicity. DFOG may be effective in inhibiting the self‑renewal capacity of SFCs derived from the SKOV3 cell line. DFOG decreased the level of phosphorylated FOXO3a protein in SKOV3 cell‑derived SFCs. The inhibition of FOXO3a expression by siRNA significantly attenuated the ability of DFOG to inhibit the self-renewal capacity of SKOV3-derived SFCs. Our results suggested that DFOG has been demonstrated to significantly inhibit the self-renewal capacity of ovarian cancer stem cells (OCSCs) through a mechanism partly dependent on the activation of FOXO3a.

希腊《分子医学报告》，2014年5月

7‑二氟甲基‑5,4' ‑二正辛基金雀异黄素可以通过FOXO3a 介导来抑制衍生自卵巢癌 SKOV3 细胞的球形细胞自我更新能力

宁映霞，李清秀，任开群，等

中国广东省广州市广州医科大学第一附属医院妇产科

癌变主要依赖于肿瘤中存在和聚集的癌症干细胞 （CSCs）。我们先前证明新型合成的金雀异黄素类似物，7‑二氟甲基‑5,4' ‑二正辛基金雀异黄素(DFOG) 诱导卵巢癌与胃癌细胞凋亡性细胞死亡。本研究表明，来源于卵巢癌细胞 SKOV3的球形细胞 （SFCs）拥有卵巢癌干细胞 (OCSLC) 的特性，包括自我更新和高致瘤性。DFOG 可有效地抑制源自 SKOV3 细胞的SFCs的自我更新能力。DFOG 降低 了SKOV3细胞衍生的SFCs的 FOXO3a 磷酸化蛋白的水平。siRNA 抑制FOXO3a 的表达明显减弱了 DFOG 抑制 SKOV3 衍生SFCs的自我更新的能力。我们的结果表明，DFOG 已被证明通过部分依赖于 FOXO3a 激活的机制，能够明显抑制卵巢癌干细胞 (OCSCs) 的自我更新能力。