Down-regulation of miR-27a might reverse multidrug resistance of esophageal squamous cell carcinoma

Dig Dis Sci. 2010 Sep;55(9):2545-51. doi: 10.1007/s10620-009-1051-6. Epub 2009 Dec 4.

Abstract

Background: So far, the miRNAs involved in multidrug resistance of esophageal cancer have not been reported.

Aims and methods: Here we have firstly investigated the roles of miR-27a in multidrug resistance of esophageal squamous cell carcinoma using MTT assay, flow cytometry assay, and reporter gene assay, etc.

Results: Down-regulation of miR-27a could confer sensitivity of both P-glycoprotein-related and P-glycoprotein-non-related drugs on esophageal cancer cells, and might promote ADR-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of ADR. Down-regulation of miR-27a could significantly decrease the expression of P-glycoprotein, Bcl-2, and the transcription of the multidrug resistance gene 1, but up-regulate the expression of Bax.

Conclusions: MiR-27a might play important roles in multidrug resistance of esophageal cancer. The further study of the biological functions of miR-27a might be helpful for developing possible strategies to treat esophageal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / pharmacology
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Doxorubicin / metabolism
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • Esophageal Neoplasms / drug therapy
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Fluorouracil / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • MicroRNAs / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Transfection
  • Vincristine / pharmacology
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism
  • bcl-2-Associated X Protein / metabolism
  • bcl-X Protein / metabolism

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • BAK1 protein, human
  • BAX protein, human
  • BCL2L1 protein, human
  • MIRN27 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • Vincristine
  • Doxorubicin
  • Cisplatin
  • Fluorouracil