Systematic Evaluation for the Influences of the SOX17/Notch Receptor Family Members on Reversing Enzalutamide Resistance in Castration-Resistant Prostate Cancer Cells

Zhongbo Du; Zhongbo Du; Zhongbo Du; Luo Li; Wei Sun; Pingyu Zhu; Pingyu Zhu; Shulin Cheng; Shulin Cheng; Xuesong Yang; Chunli Luo; Xiaodong Yu; Xiaodong Yu; Xiaohou Wu

doi:10.3389/fonc.2021.607291

Frontiers in Oncology (Mar 2021)

Systematic Evaluation for the Influences of the SOX17/Notch Receptor Family Members on Reversing Enzalutamide Resistance in Castration-Resistant Prostate Cancer Cells

Zhongbo Du,
Zhongbo Du,
Zhongbo Du,
Luo Li,
Wei Sun,
Pingyu Zhu,
Pingyu Zhu,
Shulin Cheng,
Shulin Cheng,
Xuesong Yang,
Chunli Luo,
Xiaodong Yu,
Xiaodong Yu,
Xiaohou Wu

Affiliations

Zhongbo Du: Department of Clinical Medicine, North Sichuan Medical College, Nanchong, China
Zhongbo Du: Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
Zhongbo Du: Department of Urology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Luo Li: Center for Immunology Research, Chongqing Medical University, Chongqing, China
Wei Sun: Department of Urology, Fuling Center Hospital of Chongqing, Chongqing, China
Pingyu Zhu: Department of Clinical Medicine, North Sichuan Medical College, Nanchong, China
Pingyu Zhu: Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
Shulin Cheng: Department of Clinical Medicine, North Sichuan Medical College, Nanchong, China
Shulin Cheng: Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
Xuesong Yang: Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
Chunli Luo: Key Laboratory of Diagnostics Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, China
Xiaodong Yu: Department of Clinical Medicine, North Sichuan Medical College, Nanchong, China
Xiaodong Yu: Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
Xiaohou Wu: Department of Urology, First Affiliated Hospital of Chongqing Medical University, Chongqing, China

DOI: https://doi.org/10.3389/fonc.2021.607291
Journal volume & issue: Vol. 11

Abstract

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The treatment of castration-resistant prostate cancer (CRPC) remains challenging due to the failure of androgen deprivation therapy (ADT); hence the search for other molecular therapeutic targets besides androgen receptor signaling is ongoing. This study systematically investigated the expression of SOX17 and Notch receptors in CRPC tissues and cells in vitro, showing that consistent clinical CRPC, SOX17/Notch1, and Notch4 were responsible for enzalutamide resistance in CRPC cells. The γ secretase inhibitors, BMS-708163, GSI-IX, PF-3084014, and RO4929097 abrogated the enzalutamide resistance by inhibiting Notch1 or/and Notch4 in vitro, with GSI-IX and RO4929097 being more effective than BMS-708163 and PF-3084014 in reliving bone metastasis in vivo. In conclusion, the Notch1 and Notch4 inhibitors GSI-IX and RO4929097 are promising therapeutic agents for the treatment of CRPC.

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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