Endostar Rebuilding Vascular Homeostasis and Enhancing Chemotherapy Efficacy in Cervical Cancer Treatment [post]

liming guan
2020 unpublished
Background:The incidence rate of cervical cancer is the highest in the reproductive tract, and is not sensitive to chemotherapy. An appropriate amount of antiangiogenic agents can reconstruct tumor blood vessels in a short period of time and form vascular homeostasis, increase the function of blood vessel perfusion and reverse the multidrug resistance of chemotherapy, which is also called "vascular normalization".Endostar(a recombinant human endostatin) was developed by China and as a
more » ... and as a multi-target anti-angiogenesis agent.Endostar was mainly used in the treatment of non-small cell lung cancer, fewer reported in the treatment of cervical cancer.Purpose:To determine whether endostar can rebuild tumor vascular homeostasis and enhance chemotherapy effects for patients with cervical cancer.Methods:In this study,the patients with cervical cancer within stage IIB2 were selected,endostar combined with cisplatin+paclitaxel neoadjuvant chemotherapy(NACT) before radical surgical operation was adopted, patients outcome and adverse reaction were followed up.The changes of tumor vascular structure and perfusion function before and after endostar given were evaluated by histopathology and dynamic contrast-enhanced magnetic resonance imaging(DEC-MRI). VEGF-Notch signal pathway was detected for the regulating mechanism of vascular proliferation in different groups. GraphPad Prism 6 software were used for statistical analysis of the study results.Results:Endostar enhanced short-term (2 year) overall survival(OS) ,progression free survival(PFS) rates for cervical cancer patients.All the same,endostar increased long term (5 year) OS and PFS for cervical cancer patients.Endostar therapy exhibited with mild adverse reaction.MRI showed endostar+NACT further reduce tumor volume than NACT alone.The parameters of Ktrans,Ve for DEC-MRI in endostar group exhibited obviously increase than NACT group.Tumor vascular maturation index α-SMA/CD31 in endostar group increased obviously than NACT group, correspondingly Ki67 staining for tumor proliferative rates,lymphvascular space invasion in endostar group further declined than NACT group. The genes and proteins expression of VEGFR2,Notch1,Notch1,4,Dll4,Jagged-1 were obviously down regulated in endostar group comparing to NACT group.Conclusions: Endorstar restored vascular homeostasis in cervical cancer temporarily, enhanced chemotherapeutic agents resistance in cervical cancer, increased patient overall survival ratio.The VEGF-Notch connection blocked by endostar may play a role in this effects.
doi:10.21203/rs.3.rs-61625/v1 fatcat:myxriyf4mjgnbjzs3bbgns77cu