CA916798 regulates multidrug resistance of lung cancer cells

Asian Pac J Cancer Prev. 2011;12(12):3403-8.

Abstract

Objectives: Multidrug resistance (MDR) significantly reduces the efficacy of chemotherapy for lung cancer. In this study, we characterized the significance of CA916798, a gene up-regulated in cis-dichlorodiamine platinum (CDDP)-resistant lung adenocarcinoma cells, in mediating MDR in lung cancer cells.

Methods: CA916798 was stably transfected into H446 cells with low endogenous expression of CA916798, and knocked down in A549/CDDP cells with high endogenous level of CA916798. Expression was confirmed by real-time PCR, Western immunoblotting and immunocytochemistry. Subsequent effects were examined on cellular growth, apoptosis and cell cycle progression.

Results: Ectopic expression of CA916798 in H446 cells confered enhanced resistance to multiple chemotherapeutic agents, while its reduction rendered A549/CDDP cells less resistant to chemotherapeutic agents tested. Further analysis revealed that CA916798 regulates CDDP-induced cell growth, apoptosis and cell cycle progression.

Conclusion: CA916798 may be a novel MDR-related target for lung cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology*
  • Drug Resistance, Multiple / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Male
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Rabbits
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • Cisplatin