Treatment with the Chk1 inhibitor Go6976 enhances cisplatin cytotoxicity in SCLC cells
Treatment with the Chk1 inhibitor Go6976 enhances cisplatin cytotoxicity in SCLC cells
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DOI：
10.3892/ijo.2011.1187
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发表时间：
2012-01-01
影响因子：
5.2
通讯作者：
Danson, Sarah
中科院分区：
文献类型：
--
作者：
Thompson, Ruth;Meuth, Mark;Danson, Sarah
Acquired chemoresistance is a major obstacle in successful treatment of small cell lung cancer (SCLC). DNA damage responses can potentially contribute to resistance by halting the cell cycle following exposure to therapeutic agents, thereby facilitating repair of drug-induced lesions and protecting tumour cells from death. The Chk1 protein kinase is a key regulator in this response. We analysed the status of cell cycle checkpoint proteins and the effects of the Chk1 inhibitor Go6976 on cisplatin toxicity in SCLC cell lines. IC(50)s for cisplatin were determined using the MTT assay in six SCLC cell lines. Effects on cell cycle distribution and apoptosis were determined by flow cytometry and caspase 3 activation in the presence or absence of the Chk1 inhibitor Go6976. The activation of checkpoint proteins was determined by Western blotting. Cell lines were divided into chemosensitive and chemoresistant groups on the basis of our results. While checkpoint responses were detected in these cell lines through Western blotting, some of these responses were delayed or weaker than those seen in other cell types in response to DNA damage and replication stress. Go6976 significantly (p
