A3 腺苷受体拮抗剂，截短的 Thio-Cl-IB-MECA，诱导 T24 人膀胱癌细胞凋亡。
A3 adenosine receptor antagonist, truncated Thio-Cl-IB-MECA, induces apoptosis in T24 human bladder cancer cells.
机构信息
Departments of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University Hwayang-dong 1, Gwangjin-gu, Seoul 143-701, S. Korea.
出版信息
Anticancer Res. 2010 Jul;30(7):2823-30.
BACKGROUND
Human A(3) adenosine receptor (A(3)AR) plays an essential role in several physiopathological processes. Thus far, A(3)AR-selective ligands have been evaluated as anti-inflammation and anticancer therapeutic agents. Among these ligands, truncated thio-Cl-IB-MECA is a newly reported antagonist, and its function has not been studied.
MATERIALS AND METHODS
Cell viability was measured by MTS assay. Cell cycle progression was analysed by propidium iodide (PI) flow cytometric assay. The apoptotic effects were investigated by Hoechst staining and annexin V-FITC/PI staining. The signal-transduction mechanism was explored by Western blot.
RESULTS
Truncated thio-Cl-IB-MECA induced the growth arrest of T24 cells at sub-G(1) phase and provoked apoptosis but not necrosis. Apoptotic death was mediated by the activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK).
CONCLUSION
Since truncated thio-Cl-IB-MECA induces anti-proliferation and apoptotic effects via ERK and JNK activation, it may function as an anticancer agent in human bladder cancer cells.
背景
人类 A(3) 腺苷受体 (A(3)AR) 在多种生理病理过程中发挥着重要作用。迄今为止，A(3)AR 选择性配体已被评估为抗炎和抗癌治疗药物。在这些配体中，截断的硫代-Cl-IB-MECA 是一种新报道的拮抗剂，其功能尚未得到研究。
材料和方法
通过 MTS 测定法测量细胞活力。通过碘化丙啶 (PI) 流式细胞术分析细胞周期进程。通过 Hoechst 染色和膜联蛋白 V-FITC/PI 染色研究凋亡效应。通过 Western blot 探索信号转导机制。
结果
截断的硫代-Cl-IB-MECA 诱导 T24 细胞在亚 G(1)期停滞生长并引发凋亡而不是坏死。凋亡死亡是由细胞外信号调节激酶 (ERK) 和 c-Jun N 末端激酶 (JNK) 的激活介导的。
结论
由于截断的硫代-Cl-IB-MECA 通过激活 ERK 和 JNK 诱导抗增殖和凋亡作用，因此它可能在人膀胱癌细胞中作为抗癌剂发挥作用。
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