Impact of Methadone on Cisplatin Treatment of Bladder Cancer Cells

Anticancer Res. 2018 Mar;38(3):1369-1375. doi: 10.21873/anticanres.12360.

Abstract

Background: Cisplatin-based chemotherapy is the treatment of choice for advanced bladder cancer. Since many tumor cells show inherent or acquired cisplatin resistance, research is needed to improve the therapeutic efficacy. Since the analgesic methadone is discussed as being a sensitizer for chemotherapy, we tested its effects on the cisplatin treatment of bladder cancer cells.

Materials and methods: T24 and HT-1376 bladder cancer cells were incubated with cisplatin in combination with methadone. Cytotoxicity was examined using the WST-1 viability assay and induction of apoptosis was analyzed via phase-contrast microscopy, flow cytometry, and western blot analysis.

Results: Methadone was shown to enhance the cytotoxic effects of cisplatin on T24 cells based on the induction of apoptosis. In contrast, HT-1376 cells were identified as non-responders to methadone.

Conclusion: Methadone could act as a chemosensitizer in the future treatment of advanced bladder cancer. Further research is needed to identify the underlying molecular mechanisms.

Keywords: Bladder cancer; chemosensitization; cisplatin; cytotoxicity; methadone.

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / pharmacology*
  • Drug Synergism
  • Humans
  • Methadone / pharmacology*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology

Substances

  • Analgesics, Opioid
  • Antineoplastic Agents
  • Cisplatin
  • Methadone