Ectopic expression of the WWOX gene suppresses stemness of human ovarian cancer stem cells
- Authors:
- Hong Chao Yan
- Jun Xu
- Li Sha Fang
- Ying Ying Qiu
- Xiao Man Lin
- Hong Xiang Huang
- Qiu Yu Han
View Affiliations
Affiliations: Department of Obstetrics and Gynecology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China
- Published online on: February 17, 2015 https://doi.org/10.3892/ol.2015.2971
-
Pages:
1614-1620
-
Copyright: © Yan
et al. This is an open access article distributed under the
terms of Creative
Commons Attribution License.
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Abstract
The present study aimed to investigate the effects of the WW domain‑containing oxidoreductase (WWOX) gene on the stem cell properties of human ovarian cancer stem cells. A eukaryotic expression vector containing the WWOX gene was transfected into human ovarian cancer stem cells and Western blotting was used to assess the expression of WWOX protein in the transfected cells compared with the control cells (untransfected cells and cells transfected with the empty vector). The self‑renewal abilities of these three types of stem cells was also assessed in vitro. To monitor changes in their differentiation potential, cells were cultured in medium supplemented with serum, and the expression of specific stem cell markers was determined. Drug‑sensitivity tests were used to measure the sensitivity of the stem cells to cisplatin, doxorubicin, and mitoxantrone. The cells were also transplanted into non‑obese diabetic (NOD)/severe combined immunodeficiency (SCID) mice to determine the changes in their tumorigenicity in vivo. Cells transfected with the WWOX‑expressing plasmid stably expressed WWOX protein, while no WWOX protein was detected in control cells. Compared with the two types of control cells, WWOX‑expressing stem cells manifested significantly reduced self‑renewal ability. Compared with control cells, the expression levels of stem cell markers, including CD133, CD117, ATP‑binding cassette sub‑family G member 2, Nanog, octamer‑binding transcription factor 4 and breast cancer resistance protein, were significantly lower in WWOX‑expressing cells, while the level of the differentiation marker E‑cadherin was significantly higher in WWOX‑expressing cells. Furthermore, WWOX‑expressing cells were more sensitive to treatment with cisplatin, doxorubicin and mitoxantrone. In NOD/SCID mice, the tumorigenicity of WWOX‑expressing cells was significantly lower compared with that of control cells. The results indicate that the tumor suppressor WWOX suppresses stem cell properties in cancer stem cells, including self‑renewal ability, differentiation potential, in vivo tumorigenic capability, high‑level expression of stem cell genes and multidrug resistance.
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