Zheng Shuai-Shuai, Gao Jian-Gang, Liu Zhi-Jun, Zhang Xin-Hong, Wu Shuai, Weng Bo-Wen, Wang You-Lin, Hou Si-Chuan, Jiang Bo
Department of Urology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong 266071, P.R. China.
Mol Med Rep. 2016 Feb;13(2):1845-50. doi: 10.3892/mmr.2015.4746. Epub 2015 Dec 30.
The aim of the present study was to investigate the effect of fatty acid synthase complex (FASN) on the migration capacity of bladder transitional cell carcinoma (BTCC) cells and the involvement of matrix metalloproteinase‑9 (MMP‑9) via targeting of phospho‑AKT (p‑AKT). FASN‑specific small‑interfering RNA (FASN‑siRNA) was used to inhibit FASN gene expression in the 5637 and 253J BTCC cell lines. The knockdown efficiency of FAM‑conjugated FASN‑siRNA was confirmed by fluorescence microscopy. The migratory abilities of BTCC cells were assessed using a Transwell assay. Furthermore, protein and mRNA expression of FASN, p‑AKT, AKT, and migration‑associated protein MMP‑9 were detected by western blot analysis. Treatment with FASN inhibitor Cer and FASN‑siRNA decreased the migratory capacity of bladder cancer cells and reduced the levels of p‑AKT as well as the expression of MMP‑9. These results indicated that FASN inhibition suppressed the migratory capacity of BTCC cells through suppressing AKT activation and consequently reducing MMP‑9 expression. Targeting FASN may represent a promising novel therapeutic strategy for BTCC.
本研究的目的是探讨脂肪酸合酶复合物（FASN）对膀胱移行细胞癌（BTCC）细胞迁移能力的影响，以及通过靶向磷酸化AKT（p-AKT）介导的基质金属蛋白酶-9（MMP-9）的作用。采用FASN特异性小干扰RNA（FASN-siRNA）抑制5637和253J BTCC细胞系中FASN基因的表达。通过荧光显微镜确认FAM偶联的FASN-siRNA的敲低效率。使用Transwell试验评估BTCC细胞的迁移能力。此外，通过蛋白质印迹分析检测FASN、p-AKT、AKT和迁移相关蛋白MMP-9的蛋白质和mRNA表达。用FASN抑制剂Cer和FASN-siRNA处理可降低膀胱癌细胞的迁移能力，并降低p-AKT水平以及MMP-9的表达。这些结果表明，抑制FASN可通过抑制AKT激活从而降低MMP-9表达来抑制BTCC细胞的迁移能力。靶向FASN可能是一种有前景的BTCC新型治疗策略。
