FKBP4对前列腺癌DU145细胞迁移、侵袭及凋亡的影响

Effects of FKBP4 on migration, invasion and apoptosis of prostate cancer DU145 cells

摘要:

目的 探讨他克莫司结合蛋白4（FKBP4）对前列腺癌DU145细胞迁移、侵袭及凋亡的影响。方法 基于肿瘤浸润性免疫细胞分析2.0（TIMER 2.0）数据库比较前列腺癌组织及前列腺癌旁正常组织中FKBP4的表达差异。通过实时荧光定量聚合酶链反应（qRT-PCR）及Western blotting检测不同前列腺癌细胞（DU145、PC3、LNCaP）与前列腺正常上皮细胞（RWPE-1）中FKBP4的表达。将前列腺癌DU145细胞分为3个实验组：空白对照组、si-NC组、si-FKBP4组。采用细胞划痕实验分析DU145细胞的迁移活性，Transwell实验分析DU145细胞的侵袭能力，原位末端标记法分析DU145细胞的凋亡率，Western blotting和qRT-PCR检测DU145细胞FKBP4、磷脂酰肌醇3激酶（PI3K）与蛋白激酶B（Akt）的表达。结果 TIMER 2.0数据库分析发现，与前列腺癌旁正常组织比较，FKBP4 mRNA在前列腺癌组织中表达升高（P <0.05）。与RWPE-1组（TIMER 2.0数据库人前列腺正常上皮细胞）比较，DU145组（人前列腺癌细胞DU145）、PC3组（人前列腺癌细胞PC3）、LNCaP组（人前列腺癌细胞LNCaP）的FKBP4 mRNA和蛋白相对表达量均升高（P <0.05）。与空白对照组、si-NC组比较，si-FKBP4组DU145细胞迁移能力、侵袭能力均下降，凋亡率升高（P <0.05）。与空白对照组、si-NC组比较，si-FKBP4组DU145细胞FKBP4、PI3K、Akt mRNA和蛋白相对表达量均降低（P <0.05）。结论 FKBP4在前列腺癌中表达上调，且通过PI3K/Akt信号通路影响DU145细胞的迁移、侵袭及凋亡。

Abstract:

Objective To investigate the effects of FK506-binding protein 4 (FKBP4) on the migration, invasion and apoptosis of prostate cancer DU145 cells.Methods Differences in FKBP4 expression between prostate cancer tissues and adjacent normal tissues were compared using the Tumor Immune Estimation Resource 2.0 (TIMER2.0) database. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to detect FKBP4 expression levels in different prostate cancer cell lines (DU145, PC3, LNCaP) and normal prostate epithelial cells (RWPE-1). Prostate cancer DU145 cells were divided into three experimental groups: a blank control group, an si-NC group, and an si-FKBP4 group. Cell migration activity of DU145 cells was analyzed using the cell scratch assay. Invasion capacity was assessed via the Transwell assay. The apoptosis rates were determined using TUNEL staining. The expression levels of FKBP4, phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) in DU145 cells were detected by Western blotting and qRT-PCR.Results Analysis using the TIMER2.0 database revealed that the mRNA expression levels of FKBP4 were significantly higher in prostate cancer tissues compared to adjacent normal prostate tissues (P < 0.05). Compared with the RWPE-1 group (normal human prostate epithelial cells from the TIMER 2.0 database), the relative mRNA and protein expression levels of FKBP4 were significantly increased in the DU145 group (human prostate cancer DU145 cells), PC3 group (human prostate cancer PC3 cells), and LNCaP group (human prostate cancer LNCaP cells) (all P < 0.05). Compared with the blank control group and the si-NC group, the si-FKBP4 group exhibited decreased migration and invasion abilities of DU145 cells, along with an increased apoptosis rate (P < 0.05). Furthermore, compared with the blank control group and the si-NC group, the si-FKBP4 group showed significantly reduced relative mRNA and protein expression levels of FKBP4, PI3K, and Akt in DU145 cells (P < 0.05).Conclusion FKBP4 is up-regulated in prostate cancer and influences the migration, invasion and apoptosis of DU145 cells via the PI3K/Akt signalling pathway.