書誌事項
- タイトル別名
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- Inhibition of Caspase-9 Activity in Cisplatin-resistant Head and Neck Squamous Cell Carcinoma.
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We have previously reported that cisplatin induces caspase-9 activation in head and neck squamous cell carcinoma cells (HNSCCs) in vitro, and the use of a specific inhibitor of caspase-9 blocks cisplatin-induced apoptosis in HNSCCs. Our purpose here was to determine whether HNSCCs selected for resistance to cisplatin fail to exhibit caspase-9 activation in response to cisplatin. Cisplatin-resistant HNSCCs (CRHNSCCs) were selected for growth in the presence of cisplatin. Following cisplatin treatment, no protelyzed caspase-9 subunits were detected in the CRHNSCCs, whereas proteolytic degradation of procaspase-9 was observed in parental cisplatinsensitive HNSCCs (CSHNSCCs). Using a direct enzymatic assay measuring cleavage of the synthetic peptide substrate (LEHD-AFC), caspase-9 activity in cisplatin-treated CRHNSCCs was less than that in cisplatin-treated CSHNSCCs. Because caspase-9 activation requires the release of mitochondorial cytochrome c (Cyt c) into the cytoplasm, we determined the level of cytoplasmic Cyt c in response to cisplatin treatment. Interestingly, following cisplatin treatment, the same extent of increase in cytoplasmic Cyt c was evident and the expression of Bcl-2 family proteins (Bcl-2 and Bcl-XL) remained unchanged in both CRHNSCCs and CSHNSCCs. These results suggest that in certain HNSCC cell types, inhibition of caspase-9 activity represents another mechanism of acquired cisplatin resistance. This inhibition mechanism may be independent of the release of Cyt c into the cytoplasm.
収録刊行物
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- 日本耳鼻咽喉科学会会報
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日本耳鼻咽喉科学会会報 105 (2), 152-157, 2002
一般社団法人 日本耳鼻咽喉科頭頸部外科学会
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詳細情報
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- CRID
- 1390282679984281984
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- NII論文ID
- 10008382441
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- NII書誌ID
- AN00191551
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- ISSN
- 18830854
- 00306622
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- PubMed
- 11905052
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
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- PubMed
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