Apoptosis Induced by Piroxicam plus Cisplatin Combined Treatment Is Triggered by p21 in Mesothelioma

作者：Baldi Alfonso^*; Piccolo Maria Teresa; Boccellino Maria Rosaria; Donizetti Aldo; Cardillo Irene; La Porta Raffaele; Quagliuolo Lucio; Spugnini Enrico P; Cordero Francesca; Citro Gennaro; Menegozzo Massimo; Calogero Raffaele A; Crispi Stefania

来源：PLos One, 2011, 6(8): e23569.

DOI：10.1371/journal.pone.0023569

Background: 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.
Methodology/Principal Findings: 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.
Conclusions/Significance: 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.

• 出版日期2011-8-17