Oncology Letters, 2014, 8(1):295-300.

7‑difluoromethoxyl‑5,4'‑di‑n‑octyl genistein inhibits ovarian cancer stem cell characteristics through the downregulation of FOXM1

Ying Xia Ning, Qing Xiu Li, Kai Qun Ren, et al

Department of Gynecology and Obstetrics, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China; Laboratory of Medicine Engineering, Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China

7-Difluoromethoxyl-5,4′-di-n-octylgenistein (DFOG) is a novel synthetic genistein analogue that possesses anti-cancer activity in a variety of cancers, including ovarian cancer. The objective of the present study was to investigate whether DFOG inhibits the self-renewal capacity of ovarian cancer stem-like cells (OCSLCs) and to identify its potential mechanism of action. It was found that the sphere-forming cells (SFCs) of the SKOV3 cell line exhibited a self-renewal capacity and high tumorigenicity, indicating that they possessed the properties of ovarian cancer stem cells (OCSCs). It was also shown for the first time that DFOG preferentially inhibited proliferation, self-renewal capacity and expression of stem cell markers [cluster of differentiation (CD)133, CD44 and aldehyde dehydrogenase 1 (ALDH1)] in the SFCs derived from the SKOV3 cells. These effects were accompanied by the downregulation of forkhead box M1 (FOXM1) expression. Overexpression of FOXM1 rescued the DFOG-induced downregulation of FOXM1, CD133, CD44 and ALDH1 protein expression. It also inhibited the self-renewal capacity of the SFCs derived from the SKOV3 cells. Thus, DFOG appears to inhibit the characteristics of OCSLCs by downregulating FOXM1 expression.

希腊《肿瘤学快讯》，2014年7月

7‑二氟甲基‑5,4' ‑二正辛基金雀异黄素通过下调FOXM1抑制卵巢癌干细胞的特性

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；湖南省长沙市湖南师范大学医学院医学工程实验室

7‑二氟甲基‑5,4' ‑二正辛基金雀异黄素(DFOG) 是一种新型合成的金雀异黄素衍生物，具有对各种癌症的抗肿瘤活性，包括卵巢癌。本研究的目的是探究 DFOG能否抑制卵巢癌干细胞样细胞 (OCSLCs) 的自我更新能力并确认其潜在的活性机制。我们发现SKOV3 细胞的球形细胞 （SFCs）表现出自我更新的能力和高致瘤性，表明它们具有卵巢癌干细胞 (OCSCs) 的特性。在来自 SKOV3 细胞的SFCs中，第一次证明了DFOG能够有选择性地抑制细胞增殖、 自我更新的能力和干细胞标记物的表达 [分化 (CD) 133，CD44 和醛脱氢酶 1 (ALDH1)的群落]。这些作用伴随着FOXM1 表达的下调。FOXM1的过表达挽救了DFOG 诱导的FOXM1 CD133、 CD44、 ALDH1 蛋白表达的下调。它也能抑制SKOV3 细胞衍生SFCs的自我更新能力。因此，DFOG 似乎通过下调FOXM1 的表达来抑制 OCSLCs。