A model of the development of cisplatin resistance in human small cell lung cancer xenografts

Paula B. Caffrey, Gerald D. Frenkel, Kathryn L. Mcandrew, Kenneth Marks

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background/Aim: To study the prevention of chemotherapy resistance, we have previously designed models of drug-resistant ovarian cancer. We here report an in vivo model of cisplatin-resistant small cell lung cancer (SCLC). Materials and Methods: Mice bearing H526 SCLC xenografts received intraperitoneal pretreatment with a sub-effective cisplatin dose (0.75-1.5 mg/kg) or no pretreatment (controls). Seven days later, all mice received a higher cisplatin dose (3.0 mg/kg), and tumor response was recorded. Cell cultures initiated from pretreated and control xenografts were tested for cisplatin resistance and for glutathione-S-transferase (GST) activity. Results: Pretreatment with 1.5 mg/kg cisplatin induced resistance to 3.0 mg/kg cisplatin. Cells from a pretreated tumor were cisplatin resistant and had nearly twice the GST activity as cells from a control tumor. Conclusion: Such cells may prove useful for identifying other resistance mechanisms and thus guide the selection of potential preventative agents to be tested in the in vivo model.

Original languageEnglish (US)
Pages (from-to)745-749
Number of pages5
JournalIn Vivo
Volume30
Issue number6
DOIs
StatePublished - Nov 1 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

Keywords

  • Cisplatin
  • Drug resistance
  • SCLC

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