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.

Fish oils are a rich source of polyunsaturated fatty acids, including eicosapentaenoic acid and docosahexaenoic acid, which are reported to exhibit therapeutic effects in a variety of human diseases. However, these oils are highly susceptible to degradation due to oxidation, leading to rancidity and the formation of potentially toxic reaction products. The aim of this study was to synthesize a novel emulsifier (HA-PG10-C18) by esterifying hyaluronic acid with poly(glyceryl) 10 -stearate (PG10-C18). This emulsifier was then used to formulate nanoemulsion-based delivery systems to co-deliver fish oil and coenzyme Q10 (Q10). Q10loaded fish oil-in-water nanoemulsions were fabricated, and then their physicochemical properties, digestibility, and bioaccessibility were measured. The results indicated that the environmental stability and antioxidant activity of oil droplets coated with HA-PG10-C18 surpassed those coated with PG10-C18 due to the formation of a denser interfacial layer that blocked metal ions, oxygen, and lipase. Meanwhile, the lipid digestibility and Q10 bioaccessibility of nanoemulsions formulated with HA-PG10-C18 (94.9 and 69.2%) were higher than those formulated with PG10-C18 (86.2 and 57.8%), respectively. These results demonstrated that the novel emulsifier synthesized in this study could be used to protect chemically labile fat-soluble substances from oxidative damage, while still retaining their nutritional value.