Association between mitotic spindle checkpoint impairment and susceptibility to the induction of apoptosis by anti-microtubule agents in human lung cancers
Association between mitotic spindle checkpoint impairment and susceptibility to the induction of apoptosis by anti-microtubule agents in human lung cancers
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DOI：
10.1016/s0002-9440(10)63470-0
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发表时间：
2003-09-01
影响因子：
6
通讯作者：
Takahashi, T
中科院分区：
文献类型：
--
作者：
Masuda, A;Maeno, K;Takahashi, T
抗微管剂如长春瑞滨和紫杉醇广泛用于治疗肺癌，激活有丝分裂纺锤体检查点。虽然有丝分裂纺锤体检查点的缺陷被认为在染色体不稳定性的发生中起作用，但我们先前报道了其在人肺癌细胞系中的频繁损伤。在这项研究中，我们检查了一组13种人癌细胞系，包括11种肺癌和2种其他癌症，发现在有丝分裂纺锤体检查点受损的癌细胞系和无丝分裂纺锤体检查点的癌细胞系之间，对抗微管剂诱导的细胞凋亡的抗性存在显著差异。这一发现与缺乏与DNA损伤剂顺铂的相关性形成鲜明对比。有趣的是，在有丝分裂纺锤体检查点熟练的细胞系，NCI-H460和A549中，抗微管剂诱导的细胞凋亡显示出与缩短的有丝分裂停滞相关的星形孢菌素治疗显著减少，而各种半胱天冬酶抑制剂似乎具有非常适度的作用。综上所述，这些发现表明有丝分裂纺锤体检查点可能参与了抗微管药物诱导人肺癌细胞凋亡，从而促进了对潜在机制的进一步研究。
Anti-microtubule agents such as vinorelbine and paclitaxel, which are extensively used in the treatment of lung cancers, activate Mitotic spindle checkpoint. Although defects of the mitotic spindle checkpoint are thought to play a role in the genesis of chromosome instability, we previously reported its frequent impairment in human lung cancer cell lines. in this study, we examined a panel of 13 human cancer cell lines comprising 11 lung and 2 other cancers and found a significant difference in the resistance to apoptosis induced by anti-microtubule agents between mitotic spindle checkpoint-impaired and -proficient cancer cell lines. This finding was in marked contrast to a lack of such correlation with a DNA damaging agent, cis-platin. Interestingly, anti-microtubule agent-induced apoptosis in mitotic spindle checkpoint-proficient cell lines, NCI-H460 and A549, was shown to be markedly reduced by staurosporine treatment in association with the shortened mitotic arrest, whereas various inhibitors of caspases seemed to have very modest effects. Taken together, these findings suggest the potential involvement of mitotic spindle checkpoint in the induction of apoptosis by anti-microtubule agents in human lung cancers, warranting further studies on the underlying mechanisms.