Cordycepin Combined with Doxorubicin Inhibits Triple-negative Breast Cancer by TNF Signaling Pathways

Background: Triple negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and poor prognosis. This study was designed to explore the effect of cordycepin combined with doxorubicin against TNBC, and then explore the molecular mechanism of this process. Methods: : First of all, the effect of the combination of drugs on xenograft tumor and liver of mice was carried out to study the effect of combined drug on TNBC and its toxic effect on the body. Relevant genes are obtained through the GenBank and intersected, then the molecular mechanism is explored through GO, KEGG analysis，PPI network construction and other network pharmacological methods. The results of Network pharmacology through molecular docking, immunohistochemistry and other biological experiments to verify. Results: : The results show that the combination of drugs can significantly affect the size and weight of the xenograft tumor. The tumor weight of the control group is 3.57 times that of the combined group, and the effect is more obvious than that of the single medication. The liver status, liver index, AST and ALT index of mice were not significantly different (P>0.05), indicating that the combination of drugs has no obvious toxic and side effects on the body. Through the above-mentioned series of network pharmacology methods, the final results we obtained focused on the TNF pathway and TNF-related targets such as MAP3K7, NFKB1, MAPK8 and so on.The results of molecular docking and biological verification were consistent with those of network pharmacology. Conclusions: : Cordycepin combined with doxorubicin can inhibit the growth of TNBC without obvious toxicity. The main molecular mechanism of action is to target and regulate the TNF pathway. This provides a new direction for clinical treatment of TNBC, which can effectively treat triple negative breast cancer and reduce the side effects of drugs.