P38α/β在黑色素瘤细胞辐射应急响应中的作用

The Role of P38α/β in Acute Response of Uveal Melanoma Cells Exposed to Ionizing Radiation

P38有丝分裂原激活蛋白激酶(MAPK)在肿瘤的发生发展中的作用仍然存在争议。实验结果显示,P38α/β特异性抑制剂SB202190可以显著增加黑色素瘤细胞的倍增时间、降低细胞的微核率,但对γH2AX foci的形成和克隆存活率并没有明显影响。提示P38α/β可能不影响人黑色素瘤细胞的DNA损伤修复能力及细胞的辐射敏感性,而是通过提高细胞的增殖速率、增加基因组不稳定性来促进人黑色素瘤细胞的恶性发展。

The function of P38 mitogen-activated protein kinase （MAPK） pathway in tumor initiation and promotion is still controversial. In the study, cell proliferation rate of human uveal melanoma cell lines 92-1 and OCM-1 was signifi- cantly reduced and micronucleus induction was also markedly suppressed by P38α/β specific inhibitor SB202190 regard- less of X-ray irradiation or not. However, impact on γH2AX foci and cloning efficiency were barely observed. These re- sults imply that P38MAPK might play a role in the malignant development of melanoma through promoting cell prolifera- tion and enhancing genomic instability instead of modifying DNA damage repair and radioresistance.