Study On The Effect And Mechanism Of Apatinib Alone And Combination With Anti-PD-1 Antibody In The Treatment Of Colon Cancer

Colorectal cancer is one of the common gastrointestinal malignancies,its morbidity and mortality are on the rise worldwide.The treatment of colorectal cancer is based on surgery,supplemented by chemotherapy,radiotherapy,targeted therapy,interventional therapy,and immunotherapy.But in the process of clinical diagnosis and treatment,with late diagnosed,some patients lost the opportunity to got surgery thuschemotherapy and targeted therapies are mainly treatment for these patients.Although chemotherapy combined with targeted therapy achieved good results in the treatment of colorectal cancer patients,the drug resistance phenomenon occurs after a period of clinical remission.Therefore,new candidate drugs in the treatment of colorectal cancer are urgently needed.Apatinib is a small molecule targeting vascular endothelial growth factor receptor-2,which can inhibit tumor angiogenesis.A preliminary study of apatinib found that it has a role in inhibiting tumor growth in a variety of tumor-bearing mouse models,and the ongoing clinical trials of apatinib also suggest that apatinib has a good effect in a variety of tumors.Therefore,we try to use explore the therapeutic effect of apatinib on colon cancer.In the first part,we first explored the effect of apatinib on t colon cancer cells in vitro.The results showed that apatinib could inhibit the proliferation,clone formation and migration of colon cancer cells,promote the apoptosis of colon cancer cells and block the cell cycle of colon cancer cells in G0/G1 phase.We then constructed a transplanted tumor model to examine the therapeutic effect of apatinib.The results showed that apatinib-treated mice has slower tumor growth,increased number of apoptotic cells and inhibition of tumor angiogenesis.The above results suggest that apatinib has therapeutic effect on colon cancer both in vivo and vitro.In the second part,we found that apatinib can increase the expression of PD-L1 protein both in colon cancer cells and tumor tissues,thus inhibiting the activation of T cells.Subsequently,we described the specific mechanism of PD-L1 protein expression induced by apatinib.In the third part,we constructed a mouse transplanted tumor model to explore the efficacy of apatinib combined with Anti-PD-1 antibody in the treatment of colon cancer.The results showed that apatinib combined with Anti-PD-1 antibody could inhibit the growth of transplanted tumor in mice and elevate the expression of IFN-y and GranzymeB protein in tumor tissues.Apatatinib combined with Anti-PD-1 antibody enhanced T cell function in vivo.In summary,our work explored a novel therapeutic strategy for colon cancer and discovered that apatinib inhibited the function of T cells by upregulating PD-L1 protein expression.Finally,we confirmed that the combination of apatinib and anti-PD-1 antibody could enhancethe therapeutic effec of colon cancer via elevatedthe T cell functions.but also.This study not only provides a theoretical basis for the treatment of colorectal cancer with apatinib,but also provides a theoretical basis for the treatment of colorectal cancer with apatinib combined with Anti-PD-1 antibody.It provides new candidate drugs for the treatment of colorectal cancer in clinical practice.