Objectives:Cisplatin(CDDP)is a widely used and effective basic chemotherapeutic drug for the treatment of a variety of tumors,including ovarian cancer.However,adverse side effects and acquired drug resistance are obse...Objectives:Cisplatin(CDDP)is a widely used and effective basic chemotherapeutic drug for the treatment of a variety of tumors,including ovarian cancer.However,adverse side effects and acquired drug resistance are observed in the clinical application of CDDP.Identifying a mode of administration that can alleviate side effects and reduce drug resistance has become a promising strategy to solve this problem.Methods:In this study,3 D printing technology was used to prepare a CDDP-poly(lactic-co-glycolic acid)(CDDP-PLGA)polymer compound stent,and its physicochemical properties and cytotoxicity were evaluated both in vitro and in vivo.Results:The CDDP-PLGA stent had a significant effect on cell proliferation and apoptosis and clearly decreased the size of subcutaneous tumors in nude mice,whereas the systemic side effects were mild compared with those of intraperitoneal CDDP injection.Compared with the control group,CDDP-PLGA significantly increased the mRNA and protein levels of p-glycoprotein(P<0.01;P<0.01)and decreased vascular endothelial growth factor mRNA(P<0.05)and protein levels(P<0.01),however,CDDP-PLGA significantly decreased the mR NA and protein levels of p-glycoprotein(P<0.01;P<0.01)and vascular endothelial growth factor(P<0.01;P<0.01),which are associated with chemoresistance,in subcutaneous tumor tissue.Immunohistochemistry assay results revealed that,in the CDDP-PLGA group,the staining of the proliferation-related genes Ki67 and PCNA were lightly,and the apoptosis-related gene caspase-3 stained deeply.Conclusions:PLGA biomaterials loaded with CDDP,as compared with the same amount of free CDDP,showed good efficacy in terms of cytotoxicity,as evidenced by changes in apoptosis.Continuous local CDDP release can decrease the systemic side effects of this drug and the occurrence of drug resistance and angiogenesis,and improve the therapeutic effect.This new approach may be an effective strategy for the local treatment of epithelial ovarian cancer.展开更多
基金funded by the Hubei Province Health and Family Planning Scientific Research Project(Grant No.WJ2019M179)partially supported by the National Natural Science Foundation of China(Grant No.81860276)。
文摘Objectives:Cisplatin(CDDP)is a widely used and effective basic chemotherapeutic drug for the treatment of a variety of tumors,including ovarian cancer.However,adverse side effects and acquired drug resistance are observed in the clinical application of CDDP.Identifying a mode of administration that can alleviate side effects and reduce drug resistance has become a promising strategy to solve this problem.Methods:In this study,3 D printing technology was used to prepare a CDDP-poly(lactic-co-glycolic acid)(CDDP-PLGA)polymer compound stent,and its physicochemical properties and cytotoxicity were evaluated both in vitro and in vivo.Results:The CDDP-PLGA stent had a significant effect on cell proliferation and apoptosis and clearly decreased the size of subcutaneous tumors in nude mice,whereas the systemic side effects were mild compared with those of intraperitoneal CDDP injection.Compared with the control group,CDDP-PLGA significantly increased the mRNA and protein levels of p-glycoprotein(P<0.01;P<0.01)and decreased vascular endothelial growth factor mRNA(P<0.05)and protein levels(P<0.01),however,CDDP-PLGA significantly decreased the mR NA and protein levels of p-glycoprotein(P<0.01;P<0.01)and vascular endothelial growth factor(P<0.01;P<0.01),which are associated with chemoresistance,in subcutaneous tumor tissue.Immunohistochemistry assay results revealed that,in the CDDP-PLGA group,the staining of the proliferation-related genes Ki67 and PCNA were lightly,and the apoptosis-related gene caspase-3 stained deeply.Conclusions:PLGA biomaterials loaded with CDDP,as compared with the same amount of free CDDP,showed good efficacy in terms of cytotoxicity,as evidenced by changes in apoptosis.Continuous local CDDP release can decrease the systemic side effects of this drug and the occurrence of drug resistance and angiogenesis,and improve the therapeutic effect.This new approach may be an effective strategy for the local treatment of epithelial ovarian cancer.
