Study On The Mechanism Of Matrine Injection Targeting Carbonic Anhydrase To Inhibit The Growth Of Pancreatic Cancer

Background: Although chemotherapy can prolong the survival of patients to a certain extent,the 5-year survival rate of patients with pancreatic cancer is still less than10%,and the adverse reactions caused by high-intensity chemotherapy bring great pain to patients In the process of tumor treatment,the participation of Traditional Chinese medicine plays a synergistic role in reducing toxicity.Therefore,the application of integrated traditional Chinese and Western medicine therapy can bring benefits to patients with pancreatic cancer to a certain extent.As a kind of compound treatment of many anticancer compounds,matrine injection application in tumour is gradually frequent,but its clinical effect in pancreatic cancer,as well as the effect mechanism is still in a blank stage.This study analyzes the clinical research to basic research,in-depth excavation of the matrine injection effect and mechanisms of pancreatic cancer.materials and methods: The first part: A total of 14 studies and 929 participants were included in the analysis.Compared with conventional therapy alone,matrine injection combination therapy significantly increased ORR(relative risk = 0.18,95% CI[0.12-0.24],p < 0.00001),CBR(relative risk = 0.16,95% CI [0.1-0.21],p < 0.00001)and performance status(relative risk = 0.26,95% CI [0.17– 0.35],p < 0.00001).Furthermore,matrine injection combination therapy significantly reduce ADRs,including leucopenia,nausea and vomiting,and neurotoxicity.The second part: One thousand seven hundred genes differentially expressed among pancreatic tumor and non-tumor tissues were screened out.Sixteen active components and 226 predicted target genes were identified in matrine injection.A total of 25 potential target genes of matrine injection for the treatment of pancreatic cancer were obtained.Among them,the prognostic target genes carbonic anhydrase 9(CA9)and carbonic anhydrase 12(CA12)based on the GEPIA database are differently expressed in tumors compared to adjacent normal tissue.In vitro experiments,the results of CCK-8 assay,apoptosis and cell cycle analysis,immunoblotting,and co-immunoprecipitation showed that matrine injection inhibited Capan-1 and Mia paca-2 proliferation,arrested the cell cycle at the S phase,and induced apoptosis through up-regulated CA12 and down-regulated CA9.The third part: Matrine injection inhibited the growth of subcutaneous tumors in nude mice,down-regulated the expression of CA9 protein in the tumor,and up-regulated the expression of CA12 protein in mice.Matrine injection exerted anti-tumor effects by regulating the expression of CA12 protein.