Mechanism of Guben Qingyuan Formula combined with androgen deprivation therapy inhibits castration-resistant prostate cancer by regulating the AR pathway and Wnt pathway
Objective:To explore the mechanism of Guben Qingyuan Formula combined with androgen deprivation therapy in the control of castration-resistant prostate cancer from the AR pathway of prostate cancer and the Wnt pathway of cancer stem cells.Methods:After establishing a castration-resistant prostate cancer tumor-bearing mouse model,RT-PCR and Western Blot were used to detect the expressions of AR,NKX3.1 and PSA in tumor tissues of Guben Qingyuan Formula combined with androgen deprivation therapy.Prostate cancer stem cells were sorted,and the tumor inhibition rate of Guben Qingyuan Formula combined with androgen deprivation therapy on prostate cancer stem cell-bearing mice was calculated.Then,the expressions of Wnt and β-catenin in tumor tissues were detected by Western Blot.Results:The mRNA and protein expression levels of AR and PSA in the middle and high doses of Guben Qingyuan Formula combined with androgen deprivation therapy were significantly down-regulated,and NKX3.1 was significantly up-regulated,which was significantly different from androgen deprivation therapy(P<0.05).The tumors of tumor-bearing mice inoculated with prostate cancer stem cells were larger than those of castration-resistant prostate cancer-bearing mice,and there was a statistically significant difference in tumor mass between the two groups(P<0.05).The tumor inhibition rates of the low,medium and high-dose Guben Qingyuan Formula combined with androgen deprivation therapy groups were 24.58%,36.67%,and 40.24%,respectively,which were significantly different from those of the androgen deprivation therapy group alone(P<0.05).The study showed that low,medium and high-dose Guben Qingyuan Formula combined with androgen deprivation therapy group could down-regulate the protein expression levels of Wnt and β-catenin,which were significantly different from those of the androgen deprivation therapy group alone(P<0.05).Conclusion:The mechanism of Guben Qingyuan Formula combined with androgen deprivation therapy in the control of castration-resistant prostate cancer is related to the regulation of the classical AR pathway and the Wnt/β-catenin pathway of cancer stem cells.