Blockade of Hsp27 overcomes Bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells.
Blockade of Hsp27 overcomes Bortezomib/proteasome inhibitor PS-341 resistance in lymphoma cells.
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发表时间：
2003-10
期刊：
影响因子：
11.2
通讯作者：
D. Chauhan;Guilan Li;R. Shringarpure;K. Podar;Y. Ohtake;T. Hideshima;K. Anderson
中科院分区：
文献类型：
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作者：
D. Chauhan;Guilan Li;R. Shringarpure;K. Podar;Y. Ohtake;T. Hideshima;K. Anderson
硼替佐米（PS-341）是一种选择性蛋白酶体抑制剂，可诱导多种肿瘤细胞凋亡，但其作用机制尚不清楚。用PS-341处理诱导SUDHL 6（DHL 6）而非SUDHL 4（DHL 4）淋巴瘤细胞的凋亡。微阵列分析显示，与DHL 6细胞相比，DHL 4细胞中热休克蛋白-27（Hsp 27）的RNA水平较高，这与Hsp 27蛋白表达相关。使用反义策略阻断Hsp 27恢复了DHL 4细胞中对PS-341的凋亡反应;相反，野生型Hsp 27的异位表达使PS-341敏感的DHL 6细胞对PS-341具有抗性。这些发现提供了Hsp 27赋予PS-341抗性的第一个证据。
Bortezomib (PS-341), a selective inhibitor of proteasome, induces apoptosis in various tumor cells, but its mechanism of action is unclear. Treatment with PS-341 induces apoptosis in SUDHL6 (DHL6), but not SUDHL4 (DHL4), lymphoma cells. Microarray analysis shows high RNA levels of heat shock protein-27 (Hsp27) in DHL4 versus DHL6 cells, which correlates with Hsp27 protein expression. Blocking Hsp27 using an antisense strategy restores the apoptotic response to PS-341 in DHL4 cells; conversely, ectopic expression of wild-type Hsp27 renders PS-341-sensitive DHL6 cells resistant to PS-341. These findings provide the first evidence that Hsp27 confers PS-341 resistance.