利用cDNA宏阵列鉴定参与咖啡因对骨肉瘤细胞协同抗肿瘤作用的新基因。
Identification of novel genes involved in the synergistic antitumor effect of caffeine in osteosarcoma cells using cDNA macroarray.
作者信息
Ii Sadao, Ueda Yoshimichi, Shimazaki Miyako, Katsuta Shogo, Takazawa Koutarou, Kanazawa Yoshimitsu, Tomita Katsuro, Tsuchiya Hiroyuki
机构信息
Department of Orthopaedic Surgery, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
出版信息
Anticancer Res. 2008 Mar-Apr;28(2A):645-53.
BACKGROUND
Caffeine enhances the cytocidal effects of DNA-damaging agents. This study investigated genes involved in the synergistic effect of caffeine on osteosarcoma cells using gene-profiling analysis.
MATERIALS AND METHODS
Sensitivity to cisplatin and the synergistic effect of caffeine were evaluated in five osteosarcoma cell lines with different p53 gene status. Gene expression profiles were analyzed using cDNA macroarray and verified by real-time RT-PCR.
RESULTS
The cell lines were grouped into three types with different cytotoxic patterns. Comparison of profiling data from these groups identified twelve novel genes associated with the synergistic effect of caffeine. Real-time RT-PCR analyses verified up-regulation of two apoptosis-enhancing genes and down-regulation of two interferon-inducible genes related to the synergy of caffeine.
CONCLUSION
These findings provide new insights into the molecular mechanisms of the synergistic effect of caffeine related to p53 gene status in osteosarcoma, providing candidates for an assay of responsiveness to caffeine-potentiated chemotherapy for osteosarcoma.
背景
咖啡因可增强DNA损伤剂的细胞杀伤作用。本研究利用基因谱分析，调查了参与咖啡因对骨肉瘤细胞协同作用的基因。
材料与方法
在5种具有不同p53基因状态的骨肉瘤细胞系中评估对顺铂的敏感性及咖啡因的协同作用。使用cDNA宏阵列分析基因表达谱，并通过实时逆转录聚合酶链反应进行验证。
结果
这些细胞系被分为具有不同细胞毒性模式的三种类型。对这些组的谱数据进行比较，确定了12个与咖啡因协同作用相关的新基因。实时逆转录聚合酶链反应分析证实了两个凋亡增强基因的上调以及两个与咖啡因协同作用相关的干扰素诱导基因的下调。
结论
这些发现为骨肉瘤中与p53基因状态相关的咖啡因协同作用的分子机制提供了新见解，为骨肉瘤咖啡因增强化疗反应性检测提供了候选基因。
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