PURPOSE: The aim of the present study was to evaluate the effects of piroxicam, a widely used nonsteroidal anti-inflammatory drug, alone and in combination with cisplatin (CDDP), on cell growth of mesothelioma cells. EXPERIMENTAL DESIGN: Cell proliferation, cell cycle analysis, and microarray technology were done on MSTO-211H and NCI-H2452 cells treated with piroxicam. Moreover, the effects of piroxicam and CDDP on tumor growth and survival of mouse xenograft models of mesothelioma were determined. RESULTS: Piroxicam treatment of MSTO-211H and NCI-H2452 cells resulted in a significant inhibition of proliferation. Cell cycle analysis revealed that there was an increase in the rate of apoptosis in MSTO-211H cells and an increase in the cells accumulating in G2-M in NCI-H2452. Moreover, a marked tumor growth inhibition and an extended survival of mice treated with a combination of piroxicam and CDDP in MSTO-211H cell-induced peritoneal mesotheliomas was observed. Last, GeneChip array analysis of MSTO-211H mesothelioma cell line revealed that piroxicam treatment caused up-regulation of metabolic pathway-associated genes and down-regulation of genes related to RNA processing apparatus. Of note, epidermal growth factor receptor, one of the new biological targets of chemotherapy for mesothelioma, was down-regulated and HtrA1, a serine protease recently shown to be an endogenous mediator of CDDP cytotoxicity, was up-regulated following piroxicam treatment both in vitro and in vivo. CONCLUSION: These data suggest that piroxicam sensitizes mesothelioma cells to CDDP-induced cytotoxicity by modulating the expression of several target genes. Therefore, piroxicam in combination with CDDP might potentially be useful in the treatment of patients with mesothelioma.
PURPOSE: The aim of the present study was to evaluate the effects of piroxicam, a widely used nonsteroidal anti-inflammatory drug, alone and in combination with cisplatin (CDDP), on cell growth of mesothelioma cells. EXPERIMENTAL DESIGN: Cell proliferation, cell cycle analysis, and microarray technology were done on MSTO-211H and NCI-H2452 cells treated with piroxicam. Moreover, the effects of piroxicam and CDDP on tumor growth and survival of mouse xenograft models of mesothelioma were determined. RESULTS:Piroxicam treatment of MSTO-211H and NCI-H2452 cells resulted in a significant inhibition of proliferation. Cell cycle analysis revealed that there was an increase in the rate of apoptosis in MSTO-211H cells and an increase in the cells accumulating in G2-M in NCI-H2452. Moreover, a marked tumor growth inhibition and an extended survival of mice treated with a combination of piroxicam and CDDP in MSTO-211H cell-induced peritoneal mesotheliomas was observed. Last, GeneChip array analysis of MSTO-211H mesothelioma cell line revealed that piroxicam treatment caused up-regulation of metabolic pathway-associated genes and down-regulation of genes related to RNA processing apparatus. Of note, epidermal growth factor receptor, one of the new biological targets of chemotherapy for mesothelioma, was down-regulated and HtrA1, a serine protease recently shown to be an endogenous mediator of CDDPcytotoxicity, was up-regulated following piroxicam treatment both in vitro and in vivo. CONCLUSION: These data suggest that piroxicam sensitizes mesothelioma cells to CDDP-induced cytotoxicity by modulating the expression of several target genes. Therefore, piroxicam in combination with CDDP might potentially be useful in the treatment of patients with mesothelioma.
Authors: Annette Tennstaedt; Simon Pöpsel; Linda Truebestein; Patrick Hauske; Anke Brockmann; Nina Schmidt; Inga Irle; Barbara Sacca; Christof M Niemeyer; Roland Brandt; Hanna Ksiezak-Reding; Anca Laura Tirniceriu; Rupert Egensperger; Alfonso Baldi; Leif Dehmelt; Markus Kaiser; Robert Huber; Tim Clausen; Michael Ehrmann Journal: J Biol Chem Date: 2012-04-25 Impact factor: 5.157
Authors: Velia D'Angelo; Giulia Pecoraro; Paolo Indolfi; Adriana Iannotta; Vittoria Donofrio; Maria Elena Errico; Cristiana Indolfi; Maria Ramaglia; Angela Lombardi; Martina Di Martino; Vincenzo Gigantino; Alfonso Baldi; Michele Caraglia; Antonio De Luca; Fiorina Casale Journal: J Neurooncol Date: 2014-02-04 Impact factor: 4.130
Authors: Alfonso Baldi; Maria Teresa Piccolo; Maria Rosaria Boccellino; Aldo Donizetti; Irene Cardillo; Raffaele La Porta; Lucio Quagliuolo; Enrico P Spugnini; Francesca Cordero; Gennaro Citro; Massimo Menegozzo; Raffaele A Calogero; Stefania Crispi Journal: PLoS One Date: 2011-08-17 Impact factor: 3.240