RETRACTED ARTICLE: Genistein inhibits stemness of SKOV3 cells induced by macrophages co-cultured with ovarian cancer stem-like cells through IL-8/STAT3 axis

Abstract

BackgroundRecent studies showed that macrophages co-cultured with ovarian cancer stem-like cells (OCSLCs) induced SKOV3 cell stemness via IL-8/STAT3 signaling. Genistein (GEN) demonstrates chemopreventive activity in inflammation-associated cancers. The present study aimed to examine whether and if GEN inhibits the stemness of SKOV3 and OVCA-3R cells induced by co-culture of THP-1 macrophages and SKOV3-derived OCSLCs.MethodsThe co-culture was treated with or without different concentrations (10, 20, and 40 μmol/L) of GEN for 24 h. Depletion or addition of IL-8 in Co-CM and knockdown or overexpression of STAT3 in THP-1 macrophages was performed to demonstrate the possible associated mechanisms. The combined effects of GEN and STAT3 knockdown were examined with the nude mouse modle by co-injection of SKOV3-derived OCSLCs with THP-1 macrophages.ResultsOur results showed that GEN down-regulated CD163 and p-STAT3 expression of THP-1 macrophage, decreased the levels of IL-10, increased the levels of IL-12 and nitric oxide (NO) in the conditioned medium, and reduced the clonogenic and sphere-forming capacities and the expression of CD133 and CD44 in SKOV3 cells induced by co-culture of THP-1 macrophages and OCSLCs in a dose-dependent manner. Moreover, depletion or addition of IL-8 enhanced or attenuated the effect of GEN. Additionally, knockdown or overepression of STAT3 in THP-1 macrophages potentiated or attenuated the inhibitory effects of GEN. Importantly, STAT3 overexpression retrieved the effects of IL-8 combined with GEN depletion on M2 polarization of THP-1 macrophages and stemness of SKOV3 cells induced by co-culture. The combination of GEN and STAT3 knockdown cooperatively inhibited the growth of tumors co-inoculated with OCSLCs/THP-1 macrophages in nude mice in vivo through blocking IL-8/STAT3 signaling.ConclusionsIn summary, our findings suggested that GEN can inhibit the increased M2 polarization of macrophages and stemness of ovarian cancer cells by co-culture of macrophages with OCSLCs through disrupting IL-8/STAT3 signaling axis. This assisted GEN to be as a potential chemotherapeutic agent in human ovarian cancer.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-1010-1) contains supplementary material, which is available to authorized users.

Gastric cancer-derived mesenchymal stromal cells trigger M2 macrophage polarization that promotes metastasis and EMT in gastric cancer

“…5a). Since both IL-6 and IL-8 are reported to play a paramount role in macrophage polarization 21,22 , we herein investigated the contribution of IL-6, IL-8, or IL-6 and IL-8 together to the promotion of macrophage phenotype switching by GC-MSCs. First, increased phosphorylation of JAK2 and STAT3 in macrophages polarized by GC-MSCs was observed to be partly abrogated by either IL-6- or IL-8-specific neutralizing antibody treatment as shown in Fig.…”

Flavonoids as Anticancer Agents

“…Genistein exerted influence on the expression of inflammatory-related genes in breast cancer MCF-7 (high ERα/ERβ ratio), T47D (low ERα/ERβ ratio), and MDA-MB-231 (ERα-negative) cell lines [146]. Furthermore, genistein inhibited the increased M2 polarization of macrophages and stemness of ovarian cancer SKOV3 and OVCA-3R cell lines by the co-culture of macrophages with ovarian cancer stem-like cells through disrupting the interleukin (IL)-8/STAT3 signaling axis [147]. Isoflavone daidzein downregulated the pro-inflammatory NF-kB and JNK signaling pathways in adipocyte and macrophage co-cultures [148].…”

<p>NSE from diffuse large B-cell lymphoma cells regulates macrophage polarization</p>

“…Specifically, there are some differences in M1 and M2 macrophages between murine and human 7–9. For instance, NO and Arg-1 were only expressed in murine macrophages and 12-O-tetradecanoylphorbol-13-acetate (PMA)-induced THP-1 macrophages, but not expressed in primary human monocyte-derived macrophages 9–14. Recent studies showed that tumor-associated macrophages (TAMs), predominantly M2 phenotype, are involved in tumor initiation and progression and promote neoplastic transformation by releasing factors during chronic inflammation 1,15–18.…”