title: Piroxicam and cisplatin in a mouse model of peritoneal mesothelioma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.affiliation: SAFU Department, CRS, Regina Elena Cancer Institute, Rome, Italy.
authors.forename: Enrico P
authors.initials: EP
authors.lastname: Spugnini
authors.forename: Irene
authors.initials: I
authors.lastname: Cardillo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Verdina
authors.forename: Stefania
authors.initials: S
authors.lastname: Crispi
authors.forename: Silvia
authors.initials: S
authors.lastname: Saviozzi
authors.forename: Raffaele
authors.initials: R
authors.lastname: Calogero
authors.forename: Angela
authors.initials: A
authors.lastname: Nebbioso
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Cortese
authors.forename: Rossella
authors.initials: R
authors.lastname: Galati
authors.forename: Jeremy
authors.initials: J
authors.lastname: Chien
authors.forename: Viji
authors.initials: V
authors.lastname: Shridhar
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Gennaro
authors.initials: G
authors.lastname: Citro
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
authors.forename: Ada
authors.initials: A
authors.lastname: Sacchi
authors.forename: Alfonso
authors.initials: A
authors.lastname: Baldi
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010894:Piroxicam / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D010894:Piroxicam; D002945:Cisplatin