Effects Of Zinc Complex Of 3,5-di-tert-butyl Salicylate On Breast Cancer Metastasis

Due to the lack of therapeutic targets and the characteristics of high metastasis,high infiltration,the prognosis of TNBC is poor.There is no effective treatment,only chemotherapy drugs can be used to improve the survival of patients.Chemotherapy as a means of treatment,drug resistance and drug toxicity has been a difficult problem in drug development,there are urgent needs to develop low toxicity and high efficiency anti-TNBC drugs.Salicylic acid derivatives have been used for anti-inflammatory and analgesic effects.In recent years,researchers have found that they can inhibit tumor.Murine source 4T1 breast cancer cells exhibit high metastasis and high invasion,which are highly similar to human TNBC.In this study,we used mouse 4 T1 breast cancer cell line as the experimental object to evaluate the inhibitory effect of zinc complex of 3,5-di-tert-butyl salicylate on breast cancer,and to explore the antitumor effect and mechanism of zinc complex of 3,5-di-tert-butyl salicylate.The findings are as follows:1.After treatment of 4T1 cells with different concentrations of zinc complex of 3,5-di-tert-butyl salicylate at concentrations of 0μM,10μM,25μM,50μM,and 100μM,we found that high concentration of zinc complex of 3,5-di-tert-butyl salicylate could inhibit proliferation and promote apoptosis,while low concentration of zinc complex of 3,5-di-tert-butyl salicylate inhibited cell migration and invasion.2.Western blot found that zinc complex of 3,5-di-tert-butyl salicylate significantly inhibited SRC and STAT3 phosphorylation.Meanwhile,it was observed that the phosphorylation of AKT was upregulated,and the phosphorylation of AKT was completely inhibited after the combination treatment with zinc complex of 3,5-di-tert-butyl salicylate and AKT inhibitor MK2206.3.To further explore its mechanism,all proteins were extracted from cells treated with zinc complex of 3,5-di-tert-butyl salicylate,and the proteins were analyzed by mass spectrometry.Proteins affected by the treatment are involved in protein folding and stable signaling pathways.4.4T1 cell metastasis models and in situ models were established by caudal vein injection and fat pad injection.After treatment with zinc complex of 3,5-di-tert-butyl salicylate,it was found that it could not inhibit lung metastasis of 4T1 tumors in mice.Combined treatment of zinc complex of 3,5-di-tert-butyl salicylate and AKT inhibitors also did not inhibit metastasis.The results showed Low-concentration zinc 3,5-di-tert-butylsalicylate can inhibit the proliferation and metastasis of 4T1 cells,and its mechanism is related to inhibiting the activation of SRC and STAT3;while high-concentration 3,5-di-tert-butylsalicylic acid Zinc can inhibit proliferation and promote apoptosis,which may be related to the structural composition of ribosomes and signal pathways of protein stability.However,in the mouse lung metastasis model,inhibiting breast cancer metastasis by zinc complex of 3,5-di-tert-butyl salicylate was not verified,and further research is expected.