Proteasome inhibitors synergize with tumor necrosis factor-related apoptosis-induced ligand to induce anaplastic thyroid carcinoma cell death.
Proteasome inhibitors synergize with tumor necrosis factor-related apoptosis-induced ligand to induce anaplastic thyroid carcinoma cell death.
复制标题
蛋白酶体抑制剂与肿瘤坏死因子相关的凋亡诱导配体协同作用，诱导甲状腺未分化癌细胞死亡。
DOI：
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发表时间：
2007
影响因子：
5.8
通讯作者：
R. De Maria
中科院分区：
文献类型：
--
作者：
C. Conticello;Luana Adamo;R. Giuffrida;L. Vicari;A. Zeuner;A. Eramo;Gabriele Anastasi;L. Memeo;D. Giuffrida;G. Iannolo;M. Gulisano;R. De Maria
上下文
CONTEXT
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive types of cancer characterized by complete refractoriness to multimodal treatment approaches. Therapeutic strategies based on the simultaneous use of proteasome inhibitors and death receptor ligands have been shown to induce apoptosis in several tumor types but have not yet been explored in ATC.
OBJECTIVE AND METHODS
The aim of this study was to investigate the ability of the proteasome inhibitor Bortezomib to induce apoptosis in ATC cell lines. Bortezomib was used as a single agent or in combination with TNF-related apoptosis-induced ligand (TRAIL), a member of the TNF family that selectively induces tumor cell apoptosis. The molecular effects of Bortezomib were investigated by analyzing the expression of key regulators of cell cycle and apoptosis and the activation of different apoptotic pathways.
RESULTS
Bortezomib induced apoptosis in ATC cells at doses achieved in the clinical setting, differently from conventional chemotherapeutic agents. Simultaneous treatment with low doses of Bortezomib and TRAIL had a synergistic effect in inducing massive ATC cell apoptosis. Bortezomib increased the expression of cytotoxic TRAIL receptors, p21 (WAF/CIP1) and proapoptotic second mitochondria-derived activator of caspases/direct inhibitor of apoptosis binding protein with low pI, and reduced the expression of antiapoptotic mediators such as cellular Fas-associated death domain-like IL-1beta converting enzyme inhibitory protein, Bcl-2, Bcl-X(L), and inhibitor of apoptosis-1, thus resulting in cell death induction through the mitochondrial apoptotic pathway.
CONCLUSIONS
The combination of proteasome inhibitors and TRAIL synergizes to induce the destruction of chemoresistant neoplastic thyrocytes and could represent a promising therapeutic strategy for the treatment of anaplastic thyroid carcinoma.
DOI：
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发表时间：
2003-03
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Y. Ling;L. Liebes;Jian-Dong Jiang;J. Holland;P. Elliott;J. Adams;F. Muggia;R. Perez-soler
通讯作者：
Y. Ling;L. Liebes;Jian-Dong Jiang;J. Holland;P. Elliott;J. Adams;F. Muggia;R. Perez-soler
影响因子：
11.2
作者：
Lashinger, LM;Zhu, K;McConkey, DJ
通讯作者：
McConkey, DJ