| BACKGROUNDChoriocarcinoma consists of invasive,highly vascular,and anaplastic trophoblastic tissue made up of cytotrophoblasts and syncytiotrophoblasts without villi and it is the most aggressive histologic gestational trophoblastic neoplasia.It is uniquely sensitive to chemotherapy,which is the major treatment modality for patients with high-risk disease.Regimen for chemotherapy includes EMA-CO,APE,FAEV/FAV and other therapy.Chemotherapy or surgery can maintain the cure rate of the disease by about 90%,but some patients still die due to chemotherapy resistance,inoperability,recurrence and other reasons,especially patients with drug-resistant choriocarcinoma.At present,almost 20%of drug-resistant choriocarcinoma patients die due to lack of effective treatment.The incidence of choriocarcinoma in China is high.It is urgent to find out the mechanism of drug-resistant choriocarcinoma and to find new therapeutic targets for drug-resistant patients to improve their overall survival rate.CD 105 is a member of TGF-? receptor superfamily.Previous studies have confirmed that CD 105 overexpression cells are less sensitive to chemotherapy drugs than CD 105 knock-down cells in vitro,and CD 105 mediates the resistance of choriocarcinoma through the regulation of BMP 9/Smads pathway.OBJECTIVEIn this study,we intend to verify the effect of CD 105 and its related proteins on the resistance of choriocarcinoma in vivo.By comparing the xenografts of wild-type choriocarcinoma cells,CD 105 overexpression choriocarcinoma cells and CD 105 knock-down expression choriocarcinoma cells in nude mice,we analyze the expression level of CD 105 and its related proteins in each group of transplanted tumors,through which to verify and explore the mechanism of the development of choriocarcinoma resistance in vivo.METHODS1.The suspension of wild type choriocarcinoma cells,CD 105 over-expression type choriocarcinoma cells and CD 105 knock-down type choriocarcinoma cell are diluted by gradient,and then inoculated subcutaneously in nude mice to explore the optimal concentration of tumor formation.After knowing the concentration,the nude mice model of human choriocarcinoma cell transplantation is constructed.2.The status of wild-type,CD 105 overexpression and CD 105 knock-down expression xenografts in nude mice are observed.The tumor formation of each component is recorded and the tumor formation curve are drawn according to the size of the tumor.Three types of transplanted xenografts were divided into two group randomly,the experimental group and the control group.Each nude in experimental group is injected with methotrexate intraperitoneally,while the nude in control group is injected with saline.The differences of tumor volume between the experimental group and the control group after injection are compared,and the tumor inhibition rate of each group is calculated to evaluate the sensitivity of tumor to chemotherapy drugs.3.The expression of CD 105 in serum of nude mice was detected.The expression of CD 105 and BMP9/Smads signal pathway related proteins in each group was analyzed.RESULTSThe optimal concentration of choriocarcinoma in nude mice is 107/ml,and the rate of tumor formation was 100%in each group.The growth rate of wild-type transplanted xenografts is slower than that of CD 105 overexpression type and faster than that of CD 105 knock-down type.The drug resistance of xenografts in CD 105 overexpression group is higher after methotrexate administration.The concentration of CD 105 in the serum of CD 105 overexpression group was higher than that of wild group and knock-down group.The expression levels of CD 105 and BMP9 in xenografts of wild-type group were lower than that in over expression group and higher than that in knock-down expression group.CONCLUSIONThe expression of CD 105 in serum is consistent with the drug resistance of nude,as well as the level of CD 105,BMP9 and other related proteins expressed in xenografts,which laid a foundation for the study of drugs targeted in resistance for choriocarcinoma in the future. |
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