AS602801通过下调多药耐药蛋白1（MDR1）使卵巢癌干细胞对紫杉醇敏感。

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

作者信息

Yamamoto Masahiro, Suzuki Shuhei, Togashi Keita, Sanomachi Tomomi, Seino Shizuka, Kitanaka Chifumi, Okada Masashi

机构信息

Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan

Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.

出版信息

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

DOI:10.21873/anticanres.13154

PMID:30711936

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.

摘要

背景/目的：AS602801是一种抗癌干细胞（CSC）候选药物，通过降低抗凋亡蛋白survivin的表达，使卵巢CSCs对紫杉醇和卡铂敏感。本研究的目的是检测AS602801对多药耐药蛋白1（MDR1）表达的影响。

材料与方法

使用两种卵巢CSC系A2780 CSLC和TOV-21G CSLC，通过比较AS602801和survivin抑制剂YM155的作用，研究除survivin下调以外的其他机制。在用或不用AS602801处理后筛选ATP结合盒（ABC）转运蛋白的表达，在敲低ABC转运蛋白后检测细胞对紫杉醇、卡铂和顺铂的敏感性。