2. Academic Validation
  3. Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer

Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer

  • Front Oncol. 2019 Dec 19;9:1398. doi: 10.3389/fonc.2019.01398.
Hai-Hong Zhou 1,  Xu Chen 1,  Lu-Ya Cai 1,  Xing-Wei Nan 1,  Jia-Hua Chen 1,  Xiu-Xiu Chen 1,  Yang Yang 2,  Zi-Hao Xing 2,  Meng-Ning Wei 2,  Yao Li 2,  Sheng-Te Wang 2,  Kun Liu 2,  Zhi Shi 2,  Xiao-Jian Yan 1 3
Affiliations

Affiliations

  • 1 Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 2 Guangdong Provincial Key Laboratory of Bioengineering Medicine, Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China.
  • 3 Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women's Hospital and Institute of Translation Medicine, Zhejiang University School of Medicine, Hangzhou, China.
PMID: 31921655 DOI: 10.3389/fonc.2019.01398
Abstract

Overexpression of drug efflux transport ABCB1 is correlated with multidrug resistance (MDR) among Cancer cells. Upregulation of ABCB1 accounts for the recurrence of resistance to docetaxel therapy in ovarian Cancer with poor survival. Erastin is a novel and specific small molecule that targets SLC7A11 to induce Ferroptosis. In the present research, we explored the synergistic effect of erastin and docetaxel in ovarian Cancer. We confirmed that the co-delivery of erastin with docetaxel significantly decreased cell viability, promoted cell Apoptosis, and induced cell cycle arrest at G2/M in ovarian Cancer cells with ABCB1 overexpression. Mechanistically, erastin dominantly elevated the intracellular ABCB1 substrate levels by restricting the drug-efflux activity of ABCB1 without alteration of the expression of ABCB1. Consequently, erastin can reverse ABCB1-mediated docetaxel resistance in ovarian Cancer, revealing that the combination of erastin and docetaxel may potentially offer an effective administration for chemo-resistant patients suffering from ovarian cancers.

Keywords

ABCB1; docetaxel; erastin; ferroptosis; ovarian cancer.

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