Study On The Effect Of Endostar Alginate Hydrogel On The Treatment Of Colon Cancer

Aims:In this study,we focused on the effect of Endostar hydrogel(EH)on the treatment of mice bearing colon cancer.Using EH combined with ovalbumin antigen-loaded polydopamine nanoparticles(PN-OVA)tumor vaccine to study the effect of combination therapy on OVA-MC38 tumor-bearing mice.Methods:The EH was prepared using cross-linking alginate and calcium ions by ion-crosslinking method.The in vitro and in vivo drug release of the EH was observed and the release rate in the EH was determined.Through the study of colon cancer tumor-bearing animal,we estimated the effect of EH on colon cancer,observed tumor size.Intratumoral blood vessels were stained by immunohistochemistry,and T cell subpopulations were detected by flow cytometry.The combination of EH and PN-OVA tumor vaccine(EH+PN-OVA)was used to treat OVA-MC38 tumor-bearing C57BL/6 mouse model.The anti-angiogenesis treatments combined with tumor immunotherapy were used to observe the growth inhibition rate of colon cancer.The number of microvascular was evaluated by CD31 immunohistochemistry and flow cytometry was used to assess the subpopulations of T cells in tumors,spleen,and lymph nodes.Results:Endostar in hydrogel was released in vitro for 11 days.Fluorescent label EH could be recorded in vivo for more than 14 days.In the experiment of EH in vivo to treat C57BL/6 mice bearing colon cancer,tumor growth was significantly inhibited in EH group;immunohistochemistry results showed that the microvessel density(MVD)of the EH group was significantly less than that of the others(F = 171.49,P<0.001).The qPCR results showed that the mRNA expression of hypoxia inducible factor-1?(HIF-1?)gene was significantly increased in the EH treatment group.The mRNA expression level of the junctional adhesion molecule-A(JAM-A)gene was decreased.The results of flow cytometry showed that for the treatment groups the number of CD8+ T lymphocytes in the spleens and tumors increased.The EH treatment combined with tumor vaccine for colon cancer experimental results showed in the EH60+PN-OVA group,tumor inhibition rate reached 81.33%,and the proportion of CD3+CD8+ in lymph nodes,spleen,and tumors was also increased significantly.Conclusion:We had successfully prepared sustained-release,injectable Endostar hydrogels.For treatment of tumor-bearing mice,the tumor inhibition rate(TIR)of EH group was significantly better than that of the free-Endostar group.TIR of the EH combined with the tumor vaccine treatment group was significantly superior to the EH treatment group or the tumor vaccine group.