脂肪酸合酶抑制物可抑制膀胱癌细胞中的 P-AKT 并诱导其凋亡。

Inhibition of fatty-acid synthase suppresses P-AKT and induces apoptosis in bladder cancer.

机构信息

Department of Urology, The Affiliated First People's Hospital of Shanghai Jiao Tong University, School of Medicine, Shanghai, China.

出版信息

Urology. 2012 Aug;80(2):484.e9-15. doi: 10.1016/j.urology.2012.02.046. Epub 2012 May 2.

DOI:10.1016/j.urology.2012.02.046

PMID:22554590

Abstract

OBJECTIVE

To investigate the role of fatty acid synthase (FASN) in bladder transitional cell carcinoma (BTCC).

METHODS

FASN expression was investigated in non-muscle-invasive BTCC tissue specimens by immunohistochemistry and BTCC cell lines by Western blot. After treatment with FASN-siRNA or FASN inhibitor cerulenin (Cer), the proliferation and apoptosis of BTCC cell lines 5637 and 253 J were determined by cell counting Kit-8 (CCK8) assay and flow cytometry respectively. The expression of p-AKT, cyclin D1 (CCND1), and apoptosis-related proteins were detected by Western blot.

RESULTS

High levels of FASN expression were observed in 59% (32/54) of non-muscle-invasive BTCC tissue specimens, and FASN expression was associated with histologic grade (P < .05) and recurrence (P < .05). FASN expression was high in 6 BTCC cell lines. FASN inhibitor Cer and FASN-siRNA produced the increased apoptosis and decreased proliferation of bladder cancer cells, and caused inactivity of AKT and downregulation of CCND1. Furthermore, treatment of BTCC cell lines with Cer resulted in apoptosis via the caspase-dependent pathway involving inactivation of antiapoptotic bcl-2 protein.

CONCLUSION

Our data suggest that FASN plays an important role in BTCC development. Targeting FASN may be a new therapeutic strategy for BTCC.

摘要

目的

研究脂肪酸合酶（FASN）在膀胱移行细胞癌（BTCC）中的作用。

方法

通过免疫组织化学和 BTCC 细胞系的 Western blot 检测非肌肉浸润性 BTCC 组织标本中 FASN 的表达。用 FASN-siRNA 或 FASN 抑制剂 cerulenin（Cer）处理 BTCC 细胞系 5637 和 253 J 后，分别通过细胞计数试剂盒-8（CCK8）检测和流式细胞术检测 BTCC 细胞系的增殖和凋亡。通过 Western blot 检测 p-AKT、细胞周期蛋白 D1（CCND1）和凋亡相关蛋白的表达。

结果

在 59%（32/54）的非肌肉浸润性 BTCC 组织标本中观察到 FASN 表达水平升高，FASN 表达与组织学分级（P <.05）和复发（P <.05）有关。在 6 种 BTCC 细胞系中 FASN 表达较高。FASN 抑制剂 Cer 和 FASN-siRNA 增加了膀胱癌细胞的凋亡，降低了其增殖，并导致 AKT 失活和 CCND1 下调。此外，Cer 处理 BTCC 细胞系通过 caspase 依赖性途径导致凋亡，涉及抗凋亡 bcl-2 蛋白的失活。