Zhang Hong, Rosdahl Inger
Division of Dermatology, Clinical Research Centre, Department of Biomedicine and Surgery, Linköping University, SE-581 85 Linköping, Sweden.
Cancer Lett. 2005 Jan 10;217(1):33-41. doi: 10.1016/j.canlet.2004.07.033.
All-trans-retinoic acid (atRA) exerts its effects via apoptosis and cell cycle re-distribution. However, the mechanisms behind the effects have not been fully understood. In this study, we used a model system of matched primary and metastatic melanoma cells to investigate whether expression of Id1 and p16 proteins were involved in atRA-induced apoptosis and cell cycle re-distribution. Melanoma cells were exposed to 0.1 or 10 microM atRA for 1-96 h. Apoptosis and cell cycle were measured by flow cytometry. Expression of Id1 and p16 proteins was examined by Western blotting and immunocytochemistry. After exposure to atRA we found a marked increase in apoptosis and cell cycle re-distribution in both primary and metastatic melanoma cells. Expression level of Id1 protein was decreased and the p16 was increased in a dose- and time-dependent (P<0.05) manner after treatment with atRA. Alterations of these proteins were more pronounced in the primary melanoma cells than the matched metastases (P<0.05). These data suggested that the alterations of Id1 and/or p16 proteins were involved in atRA-induced apoptosis and cell cycle re-distribution in melanoma. These expression profiles of Id1 and p16 proteins may provide molecular evidence for better chemotherapy primarily for early stages of melanoma.
全反式维甲酸（atRA）通过诱导细胞凋亡和细胞周期重新分布发挥作用。然而，其作用背后的机制尚未完全明确。在本研究中，我们使用配对的原发性和转移性黑色素瘤细胞模型系统，来研究Id1和p16蛋白的表达是否参与atRA诱导的细胞凋亡和细胞周期重新分布。将黑色素瘤细胞暴露于0.1或10微摩尔的atRA中1 - 96小时。通过流式细胞术检测细胞凋亡和细胞周期。通过蛋白质免疫印迹法和免疫细胞化学法检测Id1和p16蛋白的表达。暴露于atRA后，我们发现原发性和转移性黑色素瘤细胞的凋亡和细胞周期重新分布均显著增加。用atRA处理后，Id1蛋白表达水平呈剂量和时间依赖性降低（P<0.05），而p16蛋白表达增加。这些蛋白的变化在原发性黑色素瘤细胞中比配对的转移灶中更明显（P<0.05）。这些数据表明，Id1和/或p16蛋白的变化参与了atRA诱导的黑色素瘤细胞凋亡和细胞周期重新分布。Id1和p16蛋白的这些表达谱可能为黑色素瘤早期更好的化疗提供分子证据。
