Wu Deyao, Tao Jun, Xu Bin, Qing Weijie, Li Pengchao, Lu Qiang, Zhang Wei
Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Urol Int. 2011;87(1):105-13. doi: 10.1159/000322849. Epub 2011 May 18.
Phosphatidylinositol 3-kinase (PI3K)-AKT signaling is a well-characterized pathway involved in the control of cell proliferation, apoptosis and oncogenesis. LY294002 is a commonly used pharmacologic inhibitor which acts at the ATP-binding site of the PI3K enzyme, thus selectively inhibiting the PI3K-AKT nexus. The purpose of the present study was to examine whether PI3K inhibited by LY294002 had an effect on human bladder cancer cells.
After treatment with LY294002, MTT assay, chemosensitivity test, colony formation assay, apoptosis assay and Western blot analysis were conducted in EJ cells.
EJ cells treated with LY294002 showed significant AKT phosphorylation suppression in a dose-response manner. Also, PI3K/AKT signaling inhibitor LY294002 suppressed cell proliferation and enhanced the chemosensitivity of doxorubicin in human bladder cancer EJ cells. Furthermore, LY294002 increased cell apoptosis to doxorubicin.
The augmentation of doxorubicin with PI3K inhibitor LY294002 may resolve the multidrug resistance of bladder cancer, and this may be a new strategy for achieving tolerance for chemotherapeutic agents in bladder cancer therapy.
磷脂酰肌醇3激酶（PI3K）-AKT信号通路是一条已被充分研究的通路，参与细胞增殖、凋亡和肿瘤发生的调控。LY294002是一种常用的药物抑制剂，作用于PI3K酶的ATP结合位点，从而选择性抑制PI3K-AKT轴。本研究的目的是探讨LY294002抑制的PI3K对人膀胱癌细胞是否有影响。
用LY294002处理后，对EJ细胞进行MTT法检测、化疗敏感性试验、集落形成试验、凋亡试验和蛋白质免疫印迹分析。
用LY294002处理的EJ细胞显示出AKT磷酸化的剂量依赖性显著抑制。此外，PI3K/AKT信号抑制剂LY294002抑制人膀胱癌细胞EJ的细胞增殖并增强阿霉素的化疗敏感性。此外，LY294002增加了阿霉素诱导的细胞凋亡。
PI3K抑制剂LY294002增强阿霉素的作用可能解决膀胱癌的多药耐药问题，这可能是膀胱癌治疗中实现化疗药物耐受性的一种新策略。
