Study On The Inhibitory Effect And Mechanism Of Small Molecule Compound ZY-444 On The Growth And Metastasis Of Prostate Cancer

Objective:Prostate cancer is one of the most common malignant tumors in the male reproductive system,and its early symptoms are often not obvious,hidden and slow progress,which poses a great threat to the health of men.Whether it is traditional therapies such as endocrine therapy,radiotherapy and chemotherapy,or new therapies such as tumor vaccine and cryotherapy,the overall efficacy of prostate cancer patients is limited.Therefore,developing new and effective drugs to address current clinical drug resistance or metastatic resistance issues will help improve the overall survival and quality of life of prostate cancer patients.ZY-444 is a pyrimidine diamine compound.In previous studies,we found that it can inhibit the growth and metastasis of breast cancer and has good anti-tumor growth effect.Therefore,in this paper,we use this compound to study the growth and metastasis of prostate cancer and its mechanism.Methods:1.ZY-444 was applied to prostate cancer cells,and verify the inhibitory effect of the compound on the function of prostate cancer cells through cell proliferation experiments,clone formation experiments,migration experiments,and flow cytometry;2.After confirming that ZY-444 has a good inhibitory effect on prostate cancer with an IC₅₀ of about 2.5μM,select this concentration of ZY-444 to treat the PC3 cell line for transcriptional genome sequencing,select the genes that have a greater impact and overexpress the genes or knock down to further verify the mechanism of action of the gene in prostate cancer at the cellular and molecular levels;3.Through animal experiments,including the construction of subcutaneous xenograft models and bone orthotopic metastasis models,the inhibitory effect of ZY-444on prostate cancer in vivo was further verified.Results:1.We discovered that ZY-444,when administered to prostate cancer cells,had a considerable restraining effect on the proliferation,migration,and clone formation of these cells,as well as inducing apoptosis and reversing EMT,thereby demonstrating a superior inhibition of prostate cancer cells in comparison to growth;2.Further explore the mechanism of ZY-444 acting on prostate cancer through genome sequencing.Through bioinformatics analysis and data review,it is concluded that the increased expression of TNFAIP3 gene and the high concentration of TNF pathway may have potential significance for prostate cancer.We discovered that,upon overexpression of TNFAIP3 at the cellular level,it was capable of hindering the proliferation,migration,and epithelial mesenchymal transformation of prostate cancer cells,as well as inducing apoptosis.ZY-444’s effect on prostate cancer cells is mirrored in its inhibition of the TNF signaling pathway.However,knocking down TNFAIP3 has the opposite effect;3.In the subcutaneous xenogeneic model,both the low-concentration dose group and the high-concentration dose group significantly inhibited the growth of prostate cancer,and showed similar or even better inhibitory effects compared with the positive control paclitaxel,and had low toxicity.In the bone orthotopic model,the bone tumors treated with the compound showed a better effect of inhibiting the growth of bone tumors than the control group.Conclusion:Small molecule compound ZY-444 has significant anti-tumor activity in prostate cancer.TNFAIP3,as an important and meaningful target for ZY-444 treatment of prostate cancer,can inhibit tumor growth and metastasis through TNF signaling pathway.This study lays a foundation for the development of new candidate compounds for the treatment of prostate cancer,and also provides a new idea for cancer therapy targeting TNFAIP3,which has both theoretical and application significance.Figure[23]table[25]reference[57]...