Morphine improved the antitumor effects on MCF-7 cells in combination with 5-Fluorouracil

Biomed Pharmacother. 2014 Apr;68(3):299-305. doi: 10.1016/j.biopha.2013.09.006. Epub 2013 Oct 8.

Abstract

Background: The most frequently used opioid in cancer pain management is morphine which remains a cornerstone for the management of cancer pain, due to the largest experience existing among physicians and widely availability in a variety of formulation. Considering that analgesics on cancer pain is often under the condition of chemotherapy and 5-Fluorouracil (5-FU) is widely used today as a potent drug for the treatment of advanced cancers, whether analgesics such as morphine, interferes the chemotherapy such as 5-FU, arose as a considerable problem.

Methods: In this study, the MCF-7 breast cancer cells were used to determine the antitumor effects of the 5-FU in combination with morphine. The cell proliferation was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and the apoptosis was determined by the Annexin V/PI staining and flow cytometry. The immunocytochemistry and western blot was used to determine the Bcl-2 and Bax expression.

Results: It was shown that in MCF-7 cells, the proliferation was inhibited, the apoptosis was promoted, the Bcl-2 expression was suppressed and the Bax expression was promoted by both 5-FU alone and morphine alone, while the superior effects were achieved in combination with the two drugs.

Conclusion: These results suggest that the morphine may have the beneficial effects on the antitumor chemotherapy with 5-FU, in stead of interferential effects.

Keywords: 5-Fluorouracil; Apoptosis; Bax; Bcl-2; Morphine; Tumor.

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacology*
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / pharmacology*
  • Apoptosis / drug effects*
  • Cell Proliferation / drug effects*
  • Drug Synergism
  • Fluorouracil / administration & dosage
  • Fluorouracil / pharmacology*
  • Humans
  • Immunohistochemistry
  • MCF-7 Cells
  • Male
  • Morphine / administration & dosage
  • Morphine / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors

Substances

  • Analgesics, Opioid
  • Antimetabolites, Antineoplastic
  • Proto-Oncogene Proteins c-bcl-2
  • Morphine
  • Fluorouracil