The Study Of The Intrinsic Anti-tumor Effects Of Human Endometrial Mesenchymal Stem Cells On Human Epithelial Ovarian Cancer Cells

Objective:To investigate whether menstrual blood-derived human endometrial mesenchymal stem cells(EnSCs)endow the anti-tumor effects against human epithelial ovarian cancer(EOC)cells.Methods:Using flow cytometry(FCM)to detect the mesenchymal characteristics of EnSCs.To evaluate the differentiation ability,human mesenchymal stem cell functional identification kit was used.To imitate the paracrine effects of EnSCs on EOC cells,we collected EnSC-conditioned medium and established transwell co-culture system.CCK-8 cell viability assay,FCM and real-time PCR were used to evaluate the influence of EnSCs on viability,cell cycle progression and mitochondrial membrane potential(MMP)within EOC cells,respectively.For in vivo study,we further established a tumor-bearing nude mouse model by co-injecting EnSCs and SK-OV-3 subcutaneously.The effects of EnSCs on proliferation,apoptosis and pro-angiogenesis were evaluated by Immunohistochemistry(IHC).The expression levels of total-AKT,phospho-AKT(Ser473),PTEN and Fox03a of EOC cells were evaluated by IHC and western blotting in vivo and in vitro.Results:1)EnSCs showed the characteristics of mesenchymal stem cells and could be induced to differentiate into lipocytes,chondrocytes and osteocytes.2)In the tumor-bearing nude mouse model,EnSCs inhibited the proliferative ability and pro-angiogenesis as well as promoted apoptosis in EOC cells.3)EnSCs inhibited viability,induced GO/G1 cell cycle progression and reduced MMP within EOC cells as well as improved cisplatin-mediated killing effects on EOC cells through paracrine way.4)EnSCs significantly inhibited the expression levels of total AKT,phospho-AKT(Ser 473)and degradation of FoxO3a in EOC cells.Conclusion:EnSCs show traits of mesenchymal stem cells and trilaminar germ disc differentiation ability.EnSCs endow intrinsic anti-tumor effects against epithelial ovarian cancer cells,which are contributed to the down-regulation of AKT/FoxO3 a signaling pathway within EOC cells.