Department of Urology, Nanyang Second People's Hospital of Henan Province, Nanyang, 473000, Henan, China.
Sichuan Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, Sichuan, China.
Biomed Pharmacother. 2020 Jul;127:110223. doi: 10.1016/j.biopha.2020.110223. Epub 2020 May 12.
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.
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.
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.
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.
前列腺癌是男性最常见的肿瘤之一，导致生活质量下降。先前的研究表明，灯盏花乙素（BRE）在恶性肿瘤中具有治疗活性。然而，BRE 对前列腺癌表现出抗肿瘤作用的作用和机制在很大程度上尚不清楚。
使用 RT-qPCR、western blot 和免疫组织化学染色分别测量前列腺癌组织和细胞系中的 mRNA 和蛋白水平。使用 CCK-8 和 Transwell 测定分别评估 PC3 和 DU145 细胞中的细胞增殖、侵袭和迁移。通过体外和体内调节 PAQR4 介导的 PI3K/Akt 通路来确定 BRE 对细胞增殖和转移的影响。
PAQR4 在前列腺癌组织和细胞系中显著过表达，与不良预后呈正相关。PAQR4 敲低抑制了 PC3 和 DU145 细胞的增殖、侵袭、迁移和上皮-间充质转化（EMT）。机制上，BRE 治疗通过下调 PAQR4 并阻断 PI3K/Akt 通路，显著抑制了两种前列腺癌细胞的恶性生物学行为。体内实验表明，BRE 给药可显著抑制前列腺癌异种移植模型中的肿瘤生长和转移。
我们的研究结果表明，BRE 通过抑制 PAQR4 介导的 PI3K/Akt 通路，在前列腺癌中发挥抗肿瘤和抗转移作用，为前列腺癌的临床治疗提供了一种新的治疗药物。
