The Effect Of KAT2A On Abiraterone Resistance In Prostate Cancer Cells

Objective:To establish an abiraterone-resistant human prostate cancer cell model.Methods:LNCa P,an AR-expressed androgen-sensitive cell line,was used to establish the abiraterone-resistant model by concentration-gradient culture in vitro.IC50 of parental cells and abiraterone-resistant cells was determined by CCK-8 assay,and the resistance index RI was calculated.The growth curves of parent cells and abiraterone-resistant cells were plotted by CCK-8 assay,and the cell population doubling time was assessed.Results:After 6-month induction with a certain concentration of abiraterone,an abiraterone-resistant cell model,namely LNCa P-AAS,was established successfully by using LNCa P.According to the dose-efficiency curve,the IC50 of LNCa P-AAR is 10.73umol/L,while the IC50 of LNCa P-AAS is 1.59umol/L,and the resistance index RI of LNCa P-AAR = IC50 resistance /IC50 parent =6.75.The doubling time of LNCa PAAR cells was 38.79 h,and the doubling time of the parental(LNCa P-AAS)cells was 51.34 h.It was shown that the doubling time of LNCa P-AAR cells was shorter than that of LNCa P-AAS cells,and the proliferation rate was significantly higher in LNCa PAAR cellsConclusion:The propagation rate of LNCa P-AAR cells was significantly faster than that of their parental cells,and an abiraterone-resistant cell model was established successfully applying LNCa P.Objective:To investigate the role of KAT2 A in drug resistance of abiraterone in prostate cancer cellsMethods:The TCGA database was used to analyze the expression of KAT2 A in prostate cancer tissues and evaluate the relationship between its expression and the clinicopathological parameters of prostate cancer.Clinical specimens were collected to detect the expression levels of KAT2 A in cancerous tissues and adjacent tissues by Western blotting.Western blotting method was used to detect the changes of KAT2 A protein expression before and after abiraterone resistance in LNCa P cells.The cell proliferation levels of silenced KAT2 A and overexpressed KAT2 A were detected by cck-8.By injecting LNCa P cells into the tail vein of nude mice,a model of drugresistant tumor-bearing nude mice was established to observe the effect of silencing KAT2 A cells on tumor growth in abiraterone resistant nude mice.Results:Through the analysis of TCGA database,we found that the expression level of KAT2 A in prostate cancer tissues was significantly higher than that in normal prostate tissues and adjacent tissues.In addition,the biochemical recurrence rate of the prostate cancer patients with high expression of KAT2 A was higher than that of the lowexpression group,and the overall survival rate and relapse-free survival rate of the prostate cancer patients with high expression of KAT2 A were significantly lower than that of the low-expression group.Western blotting results showed that the expression level of KAT2 A in tumor tissues was significantly higher than that in adjacent tissues.The expression level of KAT2 A in abiraterone-resistant cells was significantly higher than that in parental cells.CCK8 showed that overexpression of KAT2 A could promote cell drug resistance,while silencing KAT2 A expression could weaken cell drug resistance.Tumor formation by tail vein injection in nude mice showed that silencing KAT2 A could significantly reduce the growth of drug-resistant tumor.Conclusion:KAT2 A was differentially expressed in prostate cancer,adjacent and normal prostate tissues.KAT2 A expression upregulation promoted the resistance of prostate cancer cells to abiraterone.