Morphine Can Inhibit the Growth of Breast Cancer MCF-7 Cells by Arresting the Cell Cycle and Inducing Apoptosis

Biol Pharm Bull. 2017 Oct 1;40(10):1686-1692. doi: 10.1248/bpb.b17-00215. Epub 2017 Jul 21.

Abstract

Morphine is widely used for relieving cancer pain in patients with advanced cancer. However, whether morphine can suppress or promote the progression of cancer in breast cancer patients receiving morphine analgesia remains unclear. Therefore, we used an in vitro model treated with morphine and naloxone to investigate the effects of morphine on breast cancer cell line MCF-7. MCF-7 cells were cultured with different concentrations (0.01 to 10 µM) of morphine at 12th, 24th, 36th, 48th, 60th and 72nd hours. Then, cell viability was measured through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell cycle and apoptosis assays were detected by flow cytometry (FCM). In addition, cell proliferation was conducted by colony formation assay. In this study, we have found that morphine (0.01 to 10 µM) could significantly reduce the cell vitality, growth and colony formation rate of MCF-7 cells, which has a certain relationship with cell cycle progression arrested at the G0/G1 and G2/M phase and MCF-7 cells apoptosis. Moreover, naloxone along with morphine could not reverse these effects, which indicates that the inhibition of MCF-7 breast cancer cell growth and proliferation by morphine could be its independent effect, not associated with opioid receptors. Morphine can inhibit cell growth by blocking the cell cycle and promote apoptosis in MCF-7 cells. Hence, morphine may be unable to promote the progression of cancer in breast cancer patients receiving morphine analgesia.

Keywords: MCF-7 cell; apoptosis; breast cancer; cell cycle; morphine.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Cell Growth Processes / drug effects
  • Cell Survival / drug effects
  • Drug Interactions
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • MCF-7 Cells
  • Morphine / administration & dosage
  • Morphine / adverse effects
  • Morphine / pharmacology*
  • Naloxone / administration & dosage
  • Naloxone / pharmacology
  • Tumor Stem Cell Assay

Substances

  • Naloxone
  • Morphine