Embedding Similarities Between Blastocyst And Cancer Cells:Fundamentals For Abortifacients Used For Cancer Metastatic Chemoprevention

Objective:The large epidemiological studies indicates that long-term administration of oral contraceptives may reduce the risk of cancers,as well as the circulation diseases,and many similarities exist between the process of blastocyst implantation and cancer cells adhesion to human umbilical vein endothelial cells(HUVECs).In this study,the model of blastocyst implantation and cancer cells adhesion to HUVECs were built to analyse the similaries between the two biosystems.The pharmacological mechanism of abortifacient to prevent cancer cells adhesion was set up by comparing the similarities of blastocyst implantation,cancer cells adhesion to endothelial cells.Methods:MTT assay was used to determine the viability of cells under varying dosage of mifepristone and metapristone;The adhesion assay was carried out to analyze the effect of mifepristone and metapristone on the JEG-3 spheroids adhesion to RL95-2 cells/matrigel,MCF-7 cells adhesion to HUVECs/matrigel;The effect of cell adhesion molecules in respond to E2P4,mifepristone and metapristone was analyzed by flow cytometry and qRT-PCR;To the invasion of JEG-3 cells and MCF-7 cells,we used qRT-PCR and Western Blot to analyze the expression of MMPs,TLMPs after the treatment of E2P4,mifepristone,metapristone for 24 hours;The wound healing assay was performed to analyze the migration of JEG-3 cells and MCF-7 cells under the treatment of E2P4,mifepristone,metapristone for 24 hours.Results:The expression of cell adhesion molecules showed many similarities in blastocyst implantation and cancer cells adhesion to HUVECs.Both blastocyst and cancer cell expressed high levels of CD47,EpCAM,E-cadherin,integrinβ1,α5,α6,sLex,both endometrial epithelial cells and HUVECs expressed high levels of integrinβ1,α3,α5,α6,ICAM-1.The combination of E2 and P4 promoted the process of blastocyst implantation and cancer cells adhesion to HUVECs.It increased the migration,invasion and adhesion ability of both blastocyst and cancer cells by increasing the expression of integrina5β1 MMPs.The abortifacient decreased the migration,invasion,and adhesion ability of both blastocyst and cancer cell by decreasing the expression of sLex,MMPs.Conclusion:The present results revealed that many similarities exist in the expression of cell adhesion molecules between the biosystem of blastocyst implantation and cancer cells adhesion to HUVECs,at the same time,the adjustment of physiological concentrations of estradiol plus progesterone on two system showed many similarities.The low concentration of mifepristone/metapristone inhibited blastocyst implantation,and inhibited cancer cells adhesion to HUVECs,at the same time,solve the problem of tumor metastasis after surgery finally.