Piroxicam and Cisplatin in a Mouse Model of Peritoneal Mesothelioma

• Published in: Clinical cancer research 2006-10, Vol.12 (20), p.6133-6143
• Main Authors: SPUGNINI, Enrico P, CARDILLO, Irene, CHIEN, Jeremy, SHRIDHAR, Viji, VINCENZI, Bruno, CITRO, Gennaro, COGNETTI, Francesco, SACCHI, Ada, BALDI, Alfonso, VERDINA, Alessandra, CRISPI, Stefania, SAVIOZZI, Silvia, CALOGERO, Raffaele, NEBBIOSO, Angela, ALTUCCI, Lucia, CORTESE, Giancarlo, GALATI, Rossella
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cell Division - drug effects; Cell Line, Tumor; Cell Survival - drug effects; cisplatin; Cisplatin - administration & dosage; Cisplatin - therapeutic use; Disease Models, Animal; EGFR; Female; GeneChip array; HtrA1; Humans; Medical sciences; mesothelioma; Mesothelioma - drug therapy; Mesothelioma - pathology; Mice; Mice, Nude; Peritoneal Neoplasms - drug therapy; Peritoneal Neoplasms - pathology; Pharmacology. Drug treatments; piroxicam; Piroxicam - administration & dosage; Piroxicam - therapeutic use
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-06-1056

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 G 2 -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.