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Updated: Jan 29, 2026

Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines
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Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines

Published on: September 10, 2014

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AS602801 Sensitizes Ovarian Cancer Stem Cells to Paclitaxel by Down-regulating MDR1

Masahiro Yamamoto1, Shuhei Suzuki2,3, Keita Togashi2,4

  • 1Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan masahiro@med.id.yamagata-u.ac.jp m-okada@med.id.yamagata-u.ac.jp.

Anticancer Research
|February 4, 2019
PubMed
Abstract

Insights

AS602801, an anti-cancer drug, enhances ovarian cancer stem cell sensitivity to paclitaxel by reducing multi-drug resistance protein 1 (MDR1) expression, independent of survivin.

Area of Science:

  • Oncology
  • Pharmacology
  • Cancer Stem Cell Biology

Background:

  • Ovarian cancer stem cells (CSCs) are resistant to conventional chemotherapy.
  • AS602801 is an investigational drug targeting cancer stem cells.
  • Survivin is an anti-apoptotic protein implicated in drug resistance.

Purpose of the Study:

  • To investigate the effect of AS602801 on multi-drug resistance protein 1 (MDR1) expression in ovarian CSCs.
  • To elucidate mechanisms of AS602801-mediated chemosensitization beyond survivin inhibition.

Main Methods:

  • Utilized two ovarian CSC lines (A2780 CSLC, TOV-21G CSLC).
  • Compared AS602801 with YM155 (survivin inhibitor).
  • Screened ATP-binding cassette (ABC) transporter expression and assessed drug sensitivity after ABC transporter knockdown.

Main Results:

  • AS602801 reduced MDR1 expression, an ABC transporter.
  • MDR1 knockdown sensitized cells to paclitaxel but not carboplatin or cisplatin.
  • AS602801's effect on paclitaxel was less survivin-dependent than its effect on carboplatin.

Conclusions:

  • AS602801 chemosensitizes ovarian CSCs to paclitaxel.
  • This sensitization is mediated, in part, by the downregulation of MDR1.
  • AS602801 offers a potential therapeutic strategy to overcome chemoresistance in ovarian cancer.
Keywords:
Drug repositioningMDR1drug repurposingdrug resistance

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