Let-7c sensitizes acquired cisplatin-resistant A549 cells by targeting ABCC2 and Bcl-XL

Pharmazie. 2013 Dec;68(12):955-61.

Abstract

Cancer cells that develop resistance to cisplatin (DDP) are a major clinical obstacle to the successful treatment of cancer, including non-small cell lung cancer (NSCLC). Recent studies have implicated dysregulation of microRNAs (miRNAs) function in chemoresistance. Here, we explored the role of let-7c in the acquisition of DDP-resistant phenotype in A549 cells. Let-7c was downregulated in A549/DDP cell compared with A549 cells. Modulation of let-7c altered the sensitivity of A549/DDP cells to DDP through regulating DDP-induced apopotis. Furthermore, ABCC2 and Bcl-XL were identified as targets of let-7c. ABCC2 and Bcl-XL knockdown increased DDP sensitivity and DDP-induced apoptosis in A549/DDP cells. In conclusion, our findings suggested for the first time that let-7c modulate DDP response in A549/DDP cells, and one of the mechanisms was through targeting ABCC2 and Bcl-XL. Thus, let-7c could be considered for potential therapeutic application for modulating DDP-based therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Benzimidazoles
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm
  • Flow Cytometry
  • Fluorescent Dyes
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / pharmacology*
  • Multidrug Resistance-Associated Proteins / drug effects*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / isolation & purification
  • Real-Time Polymerase Chain Reaction
  • Transfection
  • bcl-X Protein / drug effects*

Substances

  • 3' Untranslated Regions
  • Antineoplastic Agents
  • Benzimidazoles
  • Fluorescent Dyes
  • MicroRNAs
  • Multidrug Resistance-Associated Proteins
  • RNA, Neoplasm
  • bcl-X Protein
  • mirnlet7 microRNA, human
  • multidrug resistance-associated protein 2
  • bisbenzimide ethoxide trihydrochloride
  • Cisplatin