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Updated: Jul 1, 2025

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BBT-877, a Novel Autotaxin Inhibitor, Abrogates Drug Resistance in Epithelial Ovarian Cancer Stem Cells

Jun Se Kim1, Min Joo Shin1, Seo Yul Lee1

  • 1Department of Physiology, School of Medicine, Pusan National University, Yangsan, Republic of Korea.

Anticancer Research
|February 29, 2024
PubMed
Abstract

Insights

BBT-877, an autotaxin inhibitor, effectively targets ovarian cancer stem cells (CSCs), reducing their viability and inhibiting metastasis. Combination therapy with paclitaxel shows enhanced efficacy against drug-resistant epithelial ovarian cancer (EOC).

Area of Science:

  • Oncology
  • Cancer Stem Cell Biology
  • Pharmacology

Background:

  • Cancer stem cells (CSCs) drive poor prognosis in epithelial ovarian cancer (EOC) through drug resistance and metastasis.
  • Autotaxin (ATX) is crucial for maintaining CSC-like properties in EOC.
  • BBT-877, an ATX inhibitor, is approved for idiopathic pulmonary fibrosis but its effect on EOC CSCs is unexplored.

Purpose of the Study:

  • To investigate the efficacy of BBT-877 against ovarian CSCs.
  • To evaluate the impact of BBT-877 on drug resistance and intraperitoneal metastasis in EOC.
  • To assess the combined effect of BBT-877 and paclitaxel (PTX) in EOC models.

Main Methods:

  • Spheroid-forming CSCs were isolated from EOC cell lines (A2780, SKOV3).
  • Assays included cell viability, western blot, PCR, spheroid formation, and in vivo metastasis models.
  • Effects of BBT-877 alone and in combination with PTX were analyzed.

Main Results:

  • Spheroid-forming CSCs displayed enhanced CSC properties and paclitaxel resistance.
  • BBT-877 potently inhibited spheroid-forming CSC viability compared to adherent cells.
  • Combined BBT-877 and PTX treatment significantly reduced CSC viability and attenuated intraperitoneal metastasis in vivo.

Conclusions:

  • BBT-877 demonstrates significant anti-cancer stem cell activity in EOC.
  • Combination therapy with BBT-877 and conventional agents like PTX holds promise for treating recurrent or drug-resistant EOC.
  • BBT-877 represents a potential therapeutic strategy for overcoming EOC drug resistance and metastasis.
Keywords:
Autotaxinautotaxin inhibitorcancer stem celldrug-resistanceepithelial ovarian cancer

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