Study On The Treatment Of Endometrial Cancer With Echovirus Type 25 And Its Synergetic Effect With Small Molecule Compounds

Endometrial cancer(EC)is one of the popular malignant tumors in women.Treatment options are currently relatively limited for EC,which is easy to relapse and metastasize.Thus,there is an urgent demand to find new treatment methods.Oncolytic viruses can specifically kill tumor cells and show good effects in the treatment of various tumors.Among them,enteroviruses have many types and are easy to modify.Numerous enteroviruses have been developed into oncolytic virus drugs and entered clinical trials in recent years.Echovirus 25(Echo25)is an enterovirus which can causes hand,foot and mouth disease in infants and young children.This study carried out a feasibility study on the development of Echo25 into a new oncolytic virus,and focused on the evaluation of Echo25 and its synergetic effect with small molecule compounds on EC treatment.First,this study evaluated the killing effect of Echo25 on 21 different types of tumor in vitro and found that Echo25 has a good oncolytic activity on varieties of tumor cells,especially the EC cells.A nude mouse transplantation tumor model of human EC was further used to evaluate the oncolytic activity of Echo25 in vivo.It was found that Echo25 significantly inhibited the growth of transplanted tumors in vivo,and showed good safety in BALB/c female mice.Subsequently,the oncolytic effect of Echo25 on EC was preliminarily explored.Using Western blot and other methods,it was found that EC cells generally express attachment receptor ITGB3 and uncoating receptor FcRn of Echo25,and released DAMPs and underwent apoptosis after Echo25 infection.Finally,this study analyzed the effects of 343 small molecule compounds in combination with Echo25 in the treatment of EC in vitro,and screened out 4 potential drug candidates for use in combination with Echo25.Additionally,synergetic effect of TAK-733 or JNJ-26481585 with Echo25 on EC treatment was analyzed in-depth.In summary,this study found that Echo25 has potential as an oncolytic virus,which especially has good oncolytic activity for EC.It can be used in combination with candidate small molecule compounds to achieve synergistic effect in EC treatment,which provides a basis for developing new EC therapies.