Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
BJU Int. 2011 Jul;108(2 Pt 2):E142-9. doi: 10.1111/j.1464-410X.2010.09810.x. Epub 2010 Nov 17.
To investigate the roles of Twist1 and Y-box binding protein-1 (YB-1) and their potential as therapeutic targets in bladder cancer (BC), as both have been suggested to play important roles in tumour growth, invasion and drug resistance.
Bladder cancer cell lines (TCCsup, UMUC3, T24 and KK47 cells) were used. Twist1 and YB-1 expression levels were assessed by luciferase reporter assay, quantitative real-time polymerase chain reaction (PCR) and western blot analysis. Tumour growth and cell cycle were analysed by cell proliferation assay and flow cytometry, respectively. Invasive and motile abilities were investigated by scratch-wound test and migration assay, respectively. Cytotoxicity assay was performed to determine drug sensitivity.
The findings showed that Twist1 regulated YB-1 expression in BC cells. Both Twist1 and YB-1 were involved in cell growth, invasion, motility and resistance to cisplatin and doxorubicin, but not to 5-fluorouracil (5-FU).
The present study showed that Twist1 regulates YB-1 expression and that both Twist1 and YB-1 promote malignant potentials, including tumour growth, invasion and anti-cancer-drug resistance, indicating that both Twist1 and YB-1 are novel molecular targets in BC.
探讨 Twist1 和 Y 盒结合蛋白 1(YB-1)在膀胱癌(BC)中的作用及其作为治疗靶点的潜力,因为两者都被认为在肿瘤生长、侵袭和耐药性中发挥重要作用。
使用膀胱癌细胞系(TCCsup、UMUC3、T24 和 KK47 细胞)。通过荧光素酶报告基因检测、实时定量聚合酶链反应(PCR)和 Western blot 分析评估 Twist1 和 YB-1 的表达水平。通过细胞增殖测定和流式细胞术分别分析肿瘤生长和细胞周期。通过划痕试验和迁移试验分别研究侵袭和迁移能力。通过细胞毒性测定来确定药物敏感性。
研究结果表明,Twist1 在 BC 细胞中调节 YB-1 的表达。Twist1 和 YB-1 均参与细胞生长、侵袭、迁移以及对顺铂和阿霉素的耐药性,但不参与 5-氟尿嘧啶(5-FU)的耐药性。
本研究表明 Twist1 调节 YB-1 的表达,Twist1 和 YB-1 均促进恶性潜能,包括肿瘤生长、侵袭和抗癌药物耐药性,表明 Twist1 和 YB-1 均是 BC 的新型分子靶点。