Bae In Hwa, Kang Sung Wook, Yoon Sung Hwan, Um Hong-Duck
Laboratory of Radiation Tumor Physiology, Korea Institute of Radiological and Medical Sciences, Nowon-gu, Seoul, Korea.
Oncol Rep. 2006 May;15(5):1175-80.
Cisplatin (CDDP) is a DNA damaging agent and is widely used for treating cancer. While the role of p53 in CDDP-induced cell death has been stressed, evidence exists that CDDP can also kill p53-mutated cells. To investigate the latter mechanism, we performed a comparative study using three different human cell types, SNU-16 (a stomach cancer cell-line), U937 (a leukemic cell-line) and 293T (a kidney fibroblast cell-line), which are defective in terms of p53 activation. A focus was placed on Bcl-2 family proteins, reactive oxygen species (ROS), and mitogen-activated protein kinases. Our results suggest that the ability of CDDP to kill these cells can be mediated by JNK, p38 MAPK and ROS, but not by ERK. It was also found that CDDP can increase the ratio of pro-apoptotic/pro-survival Bcl-2 members. While the importance of these components was found to depend on cell type, JNK was commonly involved in the deaths of all cell types examined. Therefore, the JNK pathway appears to be an ideal target for the modulation of the lethal action of CDDP in multiple types of p53-mutated cells.
顺铂（CDDP）是一种DNA损伤剂，广泛用于治疗癌症。虽然p53在顺铂诱导的细胞死亡中的作用已受到关注，但有证据表明顺铂也能杀死p53突变细胞。为了研究后一种机制，我们使用三种不同的人类细胞类型进行了一项比较研究，即SNU-16（一种胃癌细胞系）、U937（一种白血病细胞系）和293T（一种肾成纤维细胞系），这些细胞在p53激活方面存在缺陷。研究重点放在Bcl-2家族蛋白、活性氧（ROS）和丝裂原活化蛋白激酶上。我们的结果表明，顺铂杀死这些细胞的能力可能由JNK、p38 MAPK和ROS介导，而不是由ERK介导。还发现顺铂可以增加促凋亡/抗生存Bcl-2成员的比例。虽然发现这些成分的重要性取决于细胞类型，但JNK普遍参与了所有检测细胞类型的死亡。因此，JNK途径似乎是调节顺铂在多种p53突变细胞中致死作用的理想靶点。
