Multidrug resistance gene-1 is a useful predictor of Paclitaxel-based chemotherapy for patients with ovarian cancer

Gynecol Oncol. 2002 Aug;86(2):171-6. doi: 10.1006/gyno.2002.6738.


Objective: The objective of this study was to determine the relationship between multidrug resistance and sensitivity to paclitaxel (PTX) in ovarian cancer.

Methods: We used human ovarian adenocarcinoma cell lines, KF, a PTX-resistant cell line (KFTx), SK-OV-3, and KOC7c. Additionally, 27 patients with ovarian cancer who had residual disease were examined. All patients underwent postoperative chemotherapy consisting of 175 mg/m(2) PTX and area under curve (AUC) 5 carboplatin. The sensitivity of the cells to PTX or cisplatin (CDDP) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. mRNA expression of multidrug resistance gene-1 (MDR-1) and multidrug resistance-associated protein-1 (MRP-1) and MRP-2 was determined by reverse transcription-polymerase chain reaction. beta-Tubulin polymerization and Bcl-2 phosphorylation were examined by Western blot analysis.

Results: Compared with KF, the IC(50) to PTX was 5.5-fold higher for KFTx, 0.3-fold for SK-OV-3, and 52.1-fold for KOC7c. The IC(50) to CDDP was 0.7-, 4.2-, and 5.8-fold, respectively. Expression of the MDR-1 gene was clearly observed in KFTx and KOC7c. Expression of MRP-1 was observed in SK-OV-3 and KOC7c. Expression of MRP-2 was detected only in KOC7c. CDDP enhanced beta-tubulin polymerization induced by PTX in CDDP-sensitive cells. Bcl-2 phosphorylation appeared after exposure to IC(50) PTX in all cells. Twenty-one patients responded to chemotherapy and six did not. Expression of the MDR-1 gene for nonresponders was significantly higher than that for responders (260.0 +/- 191.6 vs 9.3 +/- 21.8). With the cutoff value of MDR-1 expression at 100, the predictive value for chemoresponse was 96%. Expression of the MRP-1 and MRP-2 genes did not differ between nonresponders and responders.

Conclusion: MDR-1 gene expression may be a useful predictor for PTX-based chemotherapy.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor*
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Genes, MDR* / genetics
  • Humans
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins / analysis*
  • Multidrug Resistance-Associated Proteins / genetics
  • Ovarian Neoplasms / chemistry
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics*
  • Paclitaxel / therapeutic use*
  • Predictive Value of Tests
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured


  • ABCC2 protein, human
  • Biomarkers, Tumor
  • Multidrug Resistance-Associated Protein 2
  • Multidrug Resistance-Associated Proteins
  • RNA, Messenger
  • Paclitaxel