title: Prevention of carboplatin-induced resistance in human ovarian tumor xenografts by selenite.
abstract: OBJECTIVE
  We have been exploring a prevention approach to the problem of drug resistance which develops during ovarian cancer chemotherapy. We have previously described an in vivo model of the development of resistance to the chemotherapy drug cisplatin in xenografts, and the prevention of this resistance by selenium compounds. However, a different platinum-based drug, carboplatin, is frequently utilized in ovarian cancer treatment. The aim of the present study was to design a model for the induction of resistance by carboplatin in vivo.
  
  
  METHODS
  Tumors were initiated in immunodeficient mice by subcutaneous inoculation of A2780 human ovarian tumor cells. The sensitivity of the resulting tumors to therapy was determined by measuring the effect on tumor growth of a single intraperitoneal (i.p.) treatment with a high dose of carboplatin.
  
  
  RESULTS
  The growth of control tumors was completely (although temporarily) stopped by this treatment; however, a single pre-treatment with a low i.p. dose of carboplatin resulted in the rapid development of resistance to carboplatin, and cross-resistance to cisplatin. Pre-treatment with selenite in addition to carboplatin prevented the induction of resistance. When cells from these pre-treated tumors were transplanted to new animals, the derivative tumors retained the sensitive or resistant phenotype of their tumor of origin.
  
  
  CONCLUSIONS
  Selenite can prevent the induction of resistance by carboplatin in human ovarian tumors, and thus may offer an approach to extending the long-term efficacy of platinum chemotherapy.
authors.affiliation: Department of Biological and Environmental Sciences, California University of Pennsylvania, 250 University Avenue, California, PA, 15301 U.S.A. caffrey@calu.edu.
authors.forename: Paula B
authors.initials: PB
authors.lastname: Caffrey
authors.forename: Gerald D
authors.initials: GD
authors.lastname: Frenkel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D016190:Carboplatin / Q000008:administration & dosage; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D020887:Selenious Acid / Q000008:administration & dosage / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D020887:Selenious Acid; D002945:Cisplatin
keywords: Carboplatin; drug resistance; ovarian cancer; selenite; xenografts