Zinc Finger Protein 90 Knockdown Promotes Cisplatin Sensitivity via Nrf2/HO-1 Pathway in Ovarian Cancer Cell

Author:

Wu Ching-Hu1,Feng Chien-Wei12,Wang Chiu-Lin134,Wen Zhi-Hong5ORCID,Long Cheng-Yu146ORCID,Tang Feng-Hsiang17ORCID

Affiliation:

1. Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, Taiwan

2. Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 807378, Taiwan

3. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan

4. Department of Obstetrics and Gynecology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University, Kaohsiung 812015, Taiwan

5. Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 804201, Taiwan

6. Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung 807378, Taiwan

7. Department of Obstetrics and Gynecology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung 80145, Taiwan

Abstract

Our study discussed the role of Zfp90 in ovarian cancer (OC) cell lines’ sensitivity to cisplatin. We used two OC cell lines, SK-OV-3 and ES-2, to evaluate their role in cisplatin sensitization. The protein levels of p-Akt, ERK, caspase 3, Bcl-2, Bax, E-cadherin, MMP-2, MMP-9 and other drug resistance-related molecules, including Nrf2/HO-1, were discovered in the SK-OV-3 and ES-2 cells. We also used a human ovarian surface epithelial cell to compare the effect of Zfp90. Our outcomes indicated that cisplatin treatment generates reactive oxygen species (ROS) that modulate apoptotic protein expression. The anti-oxidative signal was also stimulated, which could hinder cell migration. The intervention of Zfp90 could greatly improve the apoptosis pathway and block the migrative pathway to regulate the cisplatin sensitivity in the OC cells. This study implies that the loss of function of Zfp90 might promote cisplatin sensitization in OC cells via regulating the Nrf2/HO-1 pathway to enhance cell apoptosis and inhibit the migrative effect in both SK-OV-3 and ES-2 cells.

Funder

Ministry of Science and Technology, Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung Medical University Research Center

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference65 articles.

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3. Long-term mortality among women with epithelial ovarian cancer;Dinkelspiel;Gynecol. Oncol.,2015

4. Deaths: Final data for 2012;Murphy;Natl. Vital Stat. Rep.,2015

5. Cisplatin-based chemotherapy of human cancers;Brown;J. Cancer Sci. Ther.,2019

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