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Anticancer Res. 2019 Feb;39(2):609-617. doi: 10.21873/anticanres.13154.

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

Author information

1
Department 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.
2
Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.
3
Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan.
4
Department of Ophthalmology, Yamagata University School of Medicine, Yamagata, Japan.
5
Research Institute for Promotion of Medical Sciences, Yamagata University Faculty of Medicine, Yamagata, Japan.

Abstract

BACKGROUND/AIM:

AS602801, an anti-cancer stem cell (CSC) candidate drug, sensitizes ovarian CSCs to paclitaxel and carboplatin by reducing the expression of survivin, an anti-apoptotic protein. The aim of the study was to examine the effect of AS602801 on the expression of multi drug resistance protein 1 (MDR1).

MATERIALS AND METHODS:

Using two ovarian CSC lines, A2780 CSLC and TOV-21G CSLC, mechanisms other than survivin down-regulation were examined by comparing the effects of AS602801 and YM155, an inhibitor of survivin. After screening for the expression of ATP-binding cassette (ABC) transporters with or without AS602801 treatment, the sensitivity of cells to paclitaxel, carboplatin, and cisplatin was examined following knockdown of the ABC transporter.

RESULTS:

The combinational effect of AS602801 on paclitaxel was less dependent on survivin than the effect on carboplatin. AS602801 reduced the expression of MDR1, an ABC transporter. Knockdown of MDR1 sensitized the cells to paclitaxel, but not to carboplatin or cisplatin.

CONCLUSION:

AS602801 chemosensitized ovarian CSCs to paclitaxel by reducing the expression of MDR1.

KEYWORDS:

Drug repositioning; MDR1; drug repurposing; drug resistance

PMID:
30711936
DOI:
10.21873/anticanres.13154
[Indexed for MEDLINE]

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