Abstract:
Here, we revealed the reversibility of cabazitaxel (CBZ)-induced apoptosis in PC-3 castration resistant metastatic prostate cancer cells (mCRPC) through the hallmarks of apoptosis. The recovery of PC-3 cells from apoptosis upon removal of CBZ at different recovery periods was evaluated by Annexin V, DNA damage, oxidative damage, mitochondrial membrane depolarization, and caspase activation. Our results showed that the administration of CBZ caused apoptosis for 72 h in PC-3 cells. However, recovered cells exhibited decreased nuclear damage, plasma membrane disruption, ROS level, release cytochrome c level and caspase-3 activation with upregulation of Bcl-2 expression upon removal of especially 1 nM CBZ for 24 h recovery period in PC-3 cells. Our study indicates that CBZ treated PC-3 cells can recover after apoptotic cell death. However, advanced molecular analysis should elucidate the relationship between the molecular mechanisms of recovery and taxane response or resistance in PC-3 mCRPC cells.
摘要:
这里,我们揭示了卡巴他赛(CBZ)诱导的PC-3去势耐药转移性前列腺癌细胞(mCRPC)凋亡的可逆性。通过膜联蛋白V评估在不同恢复期去除CBZ后PC-3细胞从凋亡中的恢复,DNA损伤,氧化损伤,线粒体膜去极化,和半胱天冬酶激活。我们的结果表明,CBZ的给药导致PC-3细胞凋亡72h。然而,恢复的细胞表现出减少的核损伤,质膜破裂,ROS水平,在PC-3细胞中去除特别是1nMCBZ持续24小时恢复期后,释放细胞色素c水平和caspase-3激活,上调Bcl-2表达。我们的研究表明,CBZ处理的PC-3细胞可以在凋亡细胞死亡后恢复。然而,高级分子分析应阐明PC-3mCRPC细胞中恢复的分子机制与紫杉烷反应或抗性之间的关系。