Expert Opin Ther Targets. 2011 Jul;15(7):785-8. doi: 10.1517/14728222.2011.577420. Epub 2011 Apr 9.
Several chemotherapeutic drugs interfere with assembly of the mitotic spindle of cancer cells, leading to mitotic arrest, mediated by the spindle assembly checkpoint (SAC). However, cancer cells may be SAC-deficient and survive such treatment, due to mitotic slippage. Sensing of defective spindle assembly by the SAC, causes inhibition of the anaphase-promoting complex or cyclosome (APC/C), and blocks mitotic exit, by stabilizing APC/C substrates, such as cyclin B. Mitotic slippage may occur due to residual APC/C activity and slow cyclin B degradation. Recent preclinical data suggests that targeting mitotic exit by blocking APC/C activity is a much more efficient therapeutic approach than disturbing mitotic spindle assembly.
几种化疗药物通过纺锤体组装检查点（SAC）干扰癌细胞有丝分裂纺锤体的组装，导致有丝分裂停滞。然而，由于有丝分裂滑走，癌细胞可能缺乏 SAC 并在这种治疗下存活。SAC 通过感知有缺陷的纺锤体组装来抑制后期促进复合物或环体（APC/C），并通过稳定 APC/C 底物（如细胞周期蛋白 B）来阻止有丝分裂退出。有丝分裂滑走可能是由于残留的 APC/C 活性和缓慢的细胞周期蛋白 B 降解所致。最近的临床前数据表明，通过阻断 APC/C 活性来阻止有丝分裂退出是一种比干扰有丝分裂纺锤体组装更有效的治疗方法。
