Exposure-response relationships for oxaliplatin-treated colon cancer cells

Mark N. Kirstein, Stephanie A. Root, Megan M. Moore, Katie M. Wieman, Brent W. Williams, Pamala A. Jacobson, Paul H. Marker, Todd M. Tuttle

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Data are lacking for an optimal infusion length for oxaliplatin administered intraperitoneally. Our objectives were to establish the roles of hyperthermia and an effective length of oxaliplatin treatment in maximizing antitumor activity. SW620 cells were treated for 0.5 vs. 2 h and at 37 vs. 42°C. Cytotoxicity, cell cycle analysis, subG1 and survival were assessed with the MTT assay, flow cytometry and the clonogenic assay. The IC50 for cells treated at 37°C was 2.90±0.83 μg/ml and at 42°C, 1.99±0.66 μg/ml (P=0.14). The Emax for 37°C was 93.9±2.57% and for 42°C, 97.8±1.59% (P=0.05). The subG1 fraction did not differ between cells treated at 37 and 42°C (P=0.12). The IC50 for the cells treated for 0.5 h was 10.6±0.60 μg/ml and for 2 h, 2.80±1.70 μg/ml (P=0.02). The Emax for 0.5 h was 87.9±5.13% and for 2 h, 96.6±3.35% (P=0.09). SubG1 for 0.5 h was 8.24±1.33% and for 2 h, 15.8±2.45% (P=0.02). Clonogenic assays demonstrated diminished survival when treated with low concentrations (10 μg/ml) of oxaliplatin combined with heat treatment (P=0.017) for 2 h, but not 0.5 h. Similar clonogenic assay experiments were performed with the oxaliplatin-resistant WiDr cell line, and differences in survival following oxaliplatin and heat treatment were again observed for 2 h, but not for 0.5 h (P=0.002). Drug treatment for 2 h of both SW620 and WiDr cell lines is superior to treatment for 0.5 h. Cell kill effects are reliant on treatment length; hence, the choice of time exposure must be made with a view to maintaining a balance between the cell kill effects and the clinical feasibility of treating the patient.

Original languageEnglish (US)
Pages (from-to)37-44
Number of pages8
JournalAnti-Cancer Drugs
Volume19
Issue number1
DOIs
StatePublished - Jan 1 2008

Keywords

  • Exposure-response relationship
  • Intraperitoneal
  • Oxaliplatin
  • SW620 colon carcinoma cells
  • Thermal

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