Dan S, Yamori T
Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan.
Biochem Biophys Res Commun. 2001 Jan 26;280(3):861-7. doi: 10.1006/bbrc.2000.4231.
Most anticancer drugs cause DNA strand breaks and finally induce cell cycle arrest or cell death. To identify genes involved in these effects, we examined gene expression profiles in human lung cancer A549 cells before and after adriamycin treatment, using a cDNA array technique. In this manner, we identified several up- or down-regulated genes in cells undergoing G2 arrest following adriamycin treatment; among them, cyclin B1 expression was dramatically reduced. The reduction in cyclin B1 expression and G2 arrest were also seen after treatment with etoposide and irinotecan. Previous reports have shown that overexpression of p53 represses cyclin B1 transcription. However, cisplatin neither reduced cyclin B1 expression nor induced G2 phase arrest, while it induced a comparable amount of p53 protein. These results suggest that a reduction in cyclin B1 expression plays a role in the mechanism of action of certain anticancer drugs, including adriamycin, which induce G2 arrest in cancer cells.
大多数抗癌药物会导致DNA链断裂，最终诱导细胞周期停滞或细胞死亡。为了鉴定参与这些效应的基因，我们使用cDNA阵列技术检测了阿霉素处理前后人肺癌A549细胞中的基因表达谱。通过这种方式，我们鉴定出了阿霉素处理后处于G2期停滞的细胞中几个上调或下调的基因；其中，细胞周期蛋白B1的表达显著降低。用依托泊苷和伊立替康处理后也观察到细胞周期蛋白B1表达的降低和G2期停滞。先前的报道表明，p53的过表达会抑制细胞周期蛋白B1的转录。然而，顺铂既没有降低细胞周期蛋白B1的表达，也没有诱导G2期停滞，而它诱导产生了相当数量的p53蛋白。这些结果表明，细胞周期蛋白B1表达的降低在某些抗癌药物（包括阿霉素）的作用机制中起作用，这些药物会诱导癌细胞发生G2期停滞。
