阿霉素可通过MAPK信号转导通路促进成骨肉瘤细胞凋亡

目的: 探讨阿霉素在适宜的加药浓度、作用时间下诱导成骨肉瘤细胞凋亡的分子机制.方法: 首先通过FCM,MTT等方法探讨引起成骨肉瘤细胞凋亡的最佳药物作用浓度及时间;在此条件下应用不同信号转导通路的抑制剂观察导致细胞凋亡的可能通路;最后应用Western-Blotting来检测在成骨肉瘤细胞凋亡过程中相关信号分子的表达水平及磷酸化水平的变化.结果: 0.4 mg/L阿霉素作用成骨肉瘤细胞12 h即可引起细胞凋亡,并呈时间依赖性;用p38的抑制剂SB203580和MEK4/7的抑制剂U0126可明显抑制细胞的凋亡;Western Blotting检测发现阿霉素作用于细胞后,MAPK家族成员JNK、ERK和p38等各激酶的表达水平未发生明显变化,但JNK,p38的磷酸化水平提高了ERK的磷酸化水平有所下降;用Western Blotting检测到阿霉素作用后p53蛋白的表达水平有提高.结论: 阿霉素可导致成骨肉瘤细胞凋亡,而且此凋亡过程与MAPK通路有关.

Study on the molecular mechanisms of osteosarcoma cell apoptosis induced by Adriamycin

AIM: Based on osteosarcoma cell lines,to study the molecular mechanisms of osteosarcoma cell apoptosis by appropriate density and actiontime of Adriamycin. METHODS: Firstly,depanding on the methods of FCM,MTT etc,we got the best density and actiontime of adriamycin.and then,we used several depressors of different signal transduction pathways to observe the possible pathway of osteosarcoma cell apoptosis.Finally, we observed different expression including phosphorylation and non phosphorylation of correlated signal molecules,by the methods of WesternBlot. RESULTS: We got optimal density(0.4 mg/L) and actiontime(12 h )of adriamycin; and found that MAPK pathway had something with osteosarcoma cell apoptosis; finally, we demonstrated that several signal molecules participated in MAPK pathway . CONCLUSION : The osteosarcoma cell apoptosis resulting from adriamycin might be relative to MAPK pathway.