Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma.

Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma.
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DOI:
10.1371/journal.pone.0023569
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Crispi S
Crispi S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Baldi A;Piccolo MT;Boccellino MR;Donizetti A;Cardillo I;La Porta R;Quagliuolo L;Spugnini EP;Cordero F;Citro G;Menegozzo M;Calogero RA;Crispi S

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恶性间皮瘤(MM)是一种罕见的、高度侵袭性的肿瘤,与石棉暴露有关。迄今为止,MM的化疗方案尚未被证明是绝对有效的,需要开发新的MM治疗方法。我们之前在体内研究表明,吡罗昔康/顺铂联合治疗MM,特异性地作用于细胞周期调节,触发细胞凋亡,提高生存率。我们在分子水平上分析了吡罗昔康/顺铂治疗引起的MM细胞株凋亡增加。通过全基因组分析,我们分析了单用吡罗昔康或顺铂及联合治疗后转录基因的失调。本研究表明,联合治疗后的细胞凋亡增加是由p21介导的,因为在吡罗昔康/顺铂联合治疗中,细胞凋亡的增加在p21沉默后被消除。吡罗昔康/顺铂联合治疗确定MM细胞凋亡增加,这取决于p21的表达。结果提示,吡罗昔康/顺铂联合用药可用于临床检测表达p21的肿瘤标本。
Malignant mesothelioma (MM) is a rare, highly aggressive tumor, associated to asbestos exposure. To date no chemotherapy regimen for MM has proven to be definitively curative, and new therapies for MM treatment need to be developed. We have previously shown in vivo that piroxicam/cisplatin combined treatment in MM, specifically acts on cell cycle regulation triggering apoptosis, with survival increase. We analyzed, at molecular level, the apoptotic increase caused by piroxicam/cisplatin treatment in MM cell lines. By means of genome wide analyses, we analyzed transcriptional gene deregulation both after the single piroxicam or cisplatin and the combined treatment. Here we show that apoptotic increase following combined treatment is mediated by p21, since apoptotic increase in piroxicam/cisplatin combined treatment is abolished upon p21 silencing. Piroxicam/cisplatin combined treatment determines an apoptosis increase in MM cells, which is dependent on the p21 expression. The results provided suggest that piroxicam/cisplatin combination might be tested in clinical settings in tumor specimens that express p21.
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