Breviscapine suppresses the growth and metastasis of prostate cancer through regulating PAQR4-mediated PI3K/Akt pathway

Objectives: Prostate cancer, one of the most frequently diagnosed tumors of men, leads to poor quality of life. Previous studies have shown that breviscapine (BRE) exerts therapeutic activity in malignant tumors. However, the role and mechanism of BRE exhibit an anti-tumor effect on prostate cancer are largely unknown. Methods: The mRNA and protein levels in prostate cancer tissues and cell lines were measured using RT-qPCR, western blot, and immunohistochemical staining, respectively. Cell proliferation, invasion, and migration in both PC3 and DU145 cells were evaluated using CCK-8 and Transwell assay. The effect of BRE on cell proliferation and metastasis by regulating the PAQR4-mediated PI3K/Akt pathway in vitro and in vivo was determined. Results: PAQR4 was significantly overexpressed in prostate cancer tissues and cell lines, which was positively correlated with poor prognosis. Knockdown of PAQR4 inhibited the proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) of both PC3 and DU145 cells. Mechanistically, BRE treatment significantly suppressed the malignant biological behavior of both prostate cancer cells by downregulating PAQR4 and blocking the PI3K/Akt pathway. In vivo experiments, BRE administration remarkably inhibited tumor growth and metastasis in a xenograft model of prostate cancer. Conclusion: Our findings revealed that BRE exerts anti-tumor and anti-metastasis roles in prostate cancer by inhibiting PAQR4-mediated PI3K/Akt pathway, which provides a new therapeutic agent for prostate cancer clinical treatment.