Primary Study On The Effects Of Aspirin Against The Proliferative Effect Of Platelet In Tumor

Background: In recent years,increased papers reported the application of nonsteroidal anti-inflammatory drugs(NSAIDs)for cancer prevention and treatment.In 2016,the US Preventive Services Working Group issued primary prevention guidelines on the use of NSAIDs,especially aspirin,for cardiovascular disease and colorectal cancer,and officially established the role and status of aspirin in cancer prevention.However,the mechanism of NSAIDs in preventing cancer remains obscure.Aspirin has been used as a widely used platelet inhibitor in thrombectomy for many years.In addition,thrombocytosis is reported to be associated with poor prognosis of tumors,so platelets may contribute to tumor metastasis.Although related molecular mechanisms have been revealed,the interaction among tumor-aspirin-platelet has not been reported.Methods:(1)The network pharmacology library was employed to find therapeutic target of aspirin,which was further used to perform GO enrichment analysis and pathway enrichment analysis;(2)Lung cancer and breast cancer cells-aspirin-platelets co-culture system was established to investigate the interaction among adenocarcinoma cells,aspirin and platelets in vivo;(3)The molecular mechanism of aspirin against tumors was explored by using established tumor-bearing mouse models.Result(1)Through using the co-culture system of tumor cell-aspirin-platelets,it was proved that platelets can promote the epithelial mesenchymal transition of tumor cells,while aspirin can inhibit this transformation.Additionally,the interaction existed between platelets and tumor cells that platelets can promote the distant metastasis of tumor cells,and tumor cells can also promote platelet activation;(2)The therapeutic targets of aspirin were used for GO enrichment analysis and pathway enrichment analysis,and it was found that the biological role of aspirin in vivo can be divided into three functional blocks.Additionally,pathway enrichment analysis results revealed that the effects of aspirin linked to MAPK signaling pathway,which provided ideas for follow-up trials;(3)The mouse model of breast cancer was established and aspirin can effectively inhibit the effects of platelets to promote tumor cell growth and metastasis.