Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer

Hai-Hong Zhou; Xu Chen; Lu-Ya Cai; Xing-Wei Nan; Jia-Hua Chen; Xiu-Xiu Chen; Yang Yang; Zi-Hao Xing; Meng-Ning Wei; Yao Li; Sheng-Te Wang; Kun Liu; Zhi Shi; Xiao-Jian Yan; Xiao-Jian Yan

doi:10.3389/fonc.2019.01398

Frontiers in Oncology (Dec 2019)

Erastin Reverses ABCB1-Mediated Docetaxel Resistance in Ovarian Cancer

Hai-Hong Zhou,
Xu Chen,
Lu-Ya Cai,
Xing-Wei Nan,
Jia-Hua Chen,
Xiu-Xiu Chen,
Yang Yang,
Zi-Hao Xing,
Meng-Ning Wei,
Yao Li,
Sheng-Te Wang,
Kun Liu,
Zhi Shi,
Xiao-Jian Yan,
Xiao-Jian Yan

Affiliations

Hai-Hong Zhou: Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Xu Chen: Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Lu-Ya Cai: Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Xing-Wei Nan: Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Jia-Hua Chen: Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Xiu-Xiu Chen: Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Yang Yang: 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
Zi-Hao Xing: 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
Meng-Ning Wei: 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
Yao Li: 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
Sheng-Te Wang: 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
Kun Liu: 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
Zhi Shi: 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
Xiao-Jian Yan: Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Xiao-Jian Yan: 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

DOI: https://doi.org/10.3389/fonc.2019.01398
Journal volume & issue: Vol. 9

Abstract

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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.

Published in Frontiers in Oncology

ISSN: 2234-943X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.frontiersin.org/journals/oncology/

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