【摘要】 目的　研究P2嘌呤受体激动剂ATP对不同转移性的人前列腺癌细胞亚系 1E8和 2B4的p38和c Jun氨基末端激酶 (JNK)信号传导途径的影响。方法　以常规的蛋白免疫印迹法 ,用特异识别双磷酸化p38和JNK的特异性抗体 ,检测活化的 (磷酸化的 )p38和JNK。结果　外源性ATP以时间和剂量依赖性的方式激活细胞内的p38,并且在高转移性的 1E8细胞中ATP诱导的p38活化水平明显高于不转移的 2B4细胞。但是在ATP的作用下JNK未见明显激活。P2嘌呤受体拮抗剂苏拉明(suramin)和p38抑制剂SB 2 0 35 80均可有效抑制ATP对p38的激活 ,抑制率分别为 ,1E883%和 79% ,2B481%和 6 9%。两细胞亚系中 ,G蛋白调节剂百日咳毒素均未明显影响ATP对p38的激活。结论　细胞外ATP在恶性肿瘤细胞中能够诱导激活p38信号通路 ,且p38激活水平在转移性不同的前列腺癌细胞亚系间存在差异。我们的研究为恶性肿瘤细胞生长及转移机制研究提供了有效线索。更多还原

【Abstract】 Objective To investigate the influence of P2 purinoceptor agonist ATP on p38 mitogen-activated protein kinases (MAPK) and JNK(c-Jun NH 2-terminal kinase) signaling pathway in two human prostate cancer cell sublines (1E8 and 2B4) with different metastatsis potentials. Methods Activated p38 and JNK were detected by Western blot with phospho-specific antibodies directed against the dually phosphorylated active forms of p38 or JNK. Results Exposure of 1E8 and 2B4 prostate cancer cells to ATP resulted in p38 activation in a concentration- and time-dependent manner. ATP-induced p38 activities were higher in metastatic 1E8 cells when compared with nonmetastatic 2B4 cells. JNK signaling pathway was not activated by ATP. An MEK inhibitor PD 98059 failed to inhibit ATP-induced p38 activation, while p38 inhibitor SB 203580 and P2 purinoceptor antagonist suramin effectively inhibited activation of p38, the inhibition rate being 1E8 83% and 79%,2B4 81% and 69%. The response of ATP-stimulated p38 to G-protein modulator pertussis toxin in 1E8 and 2B4 cells was not obvious. Conclusions p38 but not JNK signaling pathway can be activated by P2 purinoceptor agonist ATP. Differences of p38 activation by ATP are noted between metastatic 1E8 cells and non-metastatic 2B4 cells. These results provide instructive clues to cancer malignant growth and metastasis research.更多还原