Kugler Wilfried, Erdlenbruch Bernhard, Otten Karoline, Jendrossek Verena, Eibl Hansjörg, Lakomek Max
Universitäts-Kinderklinik, D-37099 Göttingen, Germany.
Int J Oncol. 2004 Dec;25(6):1721-7.
Erucylphosphocholine (ErPC) is a promising antineoplastic drug for the treatment of malignant brain tumors. It exerts strong anticancer activity and induces apoptosis even in chemoresistant glioma cells. In the present study, A172 and U373MG glioma cells were treated with ErPC to explore the contribution of MAP kinase family members ERK, JNK and p38 kinase to ErPC-induced cell death. The exposure to ErPC led to activation of JNK and concurrent inhibition of ERK in both cell lines. Using specific MAP kinase inhibitors we confirmed that in U373MG cells ERK was blocked and JNK was activated upon ErPC treatment. Both effects were dependent on caspase activation. In A172 cells, ErPC treatment resulted in an activation of the JNK pathway, whereas the situation with respect to ERK signalling was more complex. We conclude that inhibition of the ERK pathway by ErPC may be related to antiproliferative effects, while activation of the JNK pathway may be responsible for its pro-apoptotic action.
芥酰磷胆碱（ErPC）是一种用于治疗恶性脑肿瘤的有前景的抗肿瘤药物。它具有很强的抗癌活性，甚至能诱导化疗耐药的胶质瘤细胞凋亡。在本研究中，用ErPC处理A172和U373MG胶质瘤细胞，以探讨丝裂原活化蛋白激酶（MAP）家族成员细胞外信号调节激酶（ERK）、c-Jun氨基末端激酶（JNK）和p38激酶对ErPC诱导的细胞死亡的作用。用ErPC处理导致两种细胞系中JNK活化和ERK同时受到抑制。使用特异性MAP激酶抑制剂，我们证实，在U373MG细胞中，ErPC处理后ERK被阻断，JNK被激活。这两种效应均依赖于半胱天冬酶激活。在A172细胞中，ErPC处理导致JNK途径激活，而ERK信号传导的情况更为复杂。我们得出结论，ErPC对ERK途径的抑制可能与其抗增殖作用有关，而JNK途径的激活可能是其促凋亡作用的原因。
