A Model of the Development of Cisplatin Resistance in Human Small Cell Lung Cancer Xenografts

In Vivo. 2016;30(6):745-749. doi: 10.21873/invivo.10990.

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.

Keywords: Cisplatin; SCLC; drug resistance.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Carcinoma, Small Cell / drug therapy*
  • Carcinoma, Small Cell / pathology
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Mice
  • Time Factors
  • Treatment Outcome
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays*

Substances

  • Antineoplastic Agents
  • Cisplatin