Caspase‐8 dependent osteosarcoma cell apoptosis induced by proteasome inhibitor MG132
Caspase‐8 dependent osteosarcoma cell apoptosis induced by proteasome inhibitor MG132
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DOI：
10.1016/j.cellbi.2007.03.037
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发表时间：
2007-10
影响因子：
3.9
通讯作者：
Xiao-Bo Yan;Di-sheng Yang;Xiang Gao;Jie Feng;Zhong-li Shi;Zhaoming Ye
中科院分区：
文献类型：
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作者：
Xiao-Bo Yan;Di-sheng Yang;Xiang Gao;Jie Feng;Zhong-li Shi;Zhaoming Ye
许多研究者报道蛋白酶体抑制剂可以诱导多种癌细胞的凋亡，如乳腺癌细胞、肺癌细胞和淋巴瘤细胞。然而，蛋白酶体抑制剂对骨肉瘤细胞的作用及其机制研究较少。在这项研究中，我们发现蛋白酶体抑制剂MG132是一种有效的诱导MG‐63人骨肉瘤细胞凋亡的药物。MG132对正常人二倍体成纤维细胞无诱导凋亡作用。在MG132处理的细胞中观察到DNA片段和凋亡小体等凋亡变化，通过细胞周期分析MG132主要导致MG - 63细胞在G2-M期阻滞。RT-PCR和Western blot检测到caspase‐8激活增加，p27Kip1积累，Bax: Bcl‐2比例增加。未观察到caspase‐3和caspase‐9的活化。这表明MG132在MG63细胞中诱导的凋亡是caspase‐8依赖性的，p27和bcl‐2家族相关。
Many researchers have reported that proteasome inhibitors could induce apoptosis in a variety of cancer cells, such as breast cancer cell, lung cancer cell, and lymphoma cell. However, the effect of proteasome inhibitors on osteocsarcoma cells and the mechanisms are seldom studied. In this study, we found proteasome inhibitor MG132 was an effective inducer of apoptosis in human osteosarcoma MG‐63 cells. On normal human diploid fibroblast cells, MG132 did not show any apoptosis‐inducing effects. Apoptotic changes such as DNA fragment and apoptotic body were observed in MG132‐treated cells and MG132 mostly caused MG‐63 cell arrest at G2–M‐phase by cell cycle analysis. Increased activation of caspase‐8, accumulation of p27Kip1, and an increased ratio of Bax: Bcl‐2 were detected by RT—PCR and Western blot analysis. Activation of caspase‐3 and caspase‐9 were not observed. This suggests that the apoptosis induced by MG132 in MG63 cells is caspase‐8 dependent, p27 and bcl‐2 family related.