ATP7B antisense oligodeoxynucleotides increase the cisplatin sensitivity of human ovarian cancer cell line SKOV3ipl

Int J Gynecol Cancer. 2008 Jul-Aug;18(4):718-22. doi: 10.1111/j.1525-1438.2007.01085.x. Epub 2007 Oct 18.

Abstract

The objective of this study was to investigate the effect of ATP7B antisense oligodeoxynucleotides (ASODNs) on regulating the sensitivity to cisplatin in ovarian carcinoma cell line SKOV3ip1. The ATP7B ASODNs and the corresponding sense oligodeoxynucleotide (SODN) as control were transfected into SKOV3ip1 cells by lipofectamine-2000. The changes of ATP7B were detected by reverse transcription-polymerase chain reaction, flow cytometry, and Western blotting. The survival rate of the SKOV3ip1 cells was assessed by MTT assay. Compared with nontransfected cell, the transfer of ASODN/lipofectin (LF) into SKOV3ip1 cells resulted in (1) 73.70% and 48.30% reduction of ATP7B in messenger RNA and protein, respectively, (2) an obviously decreased intracellular fluorescence intensity from 79.42 to 50.87 (P < 0.01), and (3) a decreased IC(50) value for cisplatin from 126.63 to 80.90 micromol/L (P < 0.01), while no significant changes were detected for groups treated with SODN/LF and LF only. ASODN transfection can inhibit the expression of ATP7B and increase the cisplatin sensitivity in SKOV3ip1 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors*
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma / drug therapy*
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cation Transport Proteins / antagonists & inhibitors*
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Cell Line, Tumor
  • Cisplatin / administration & dosage*
  • Copper-Transporting ATPases
  • Drug Evaluation, Preclinical
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / genetics
  • Drug Synergism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Oligodeoxyribonucleotides, Antisense / administration & dosage*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • RNA, Messenger / metabolism
  • Transfection

Substances

  • Cation Transport Proteins
  • Oligodeoxyribonucleotides, Antisense
  • RNA, Messenger
  • Adenosine Triphosphatases
  • ATP7B protein, human
  • Copper-Transporting ATPases
  • Cisplatin