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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

TBOPP, a DOCK1 Inhibitor, Potentiates Cisplatin Efficacy in Breast Cancer by Regulating Twist-mediated EMT

Author(s): Xin Chen, Zhenbang Zhou, Pengting Tang, Feiya Du, Shuqian Wang, Jia Yao, Shufen Zhang, Jiajing Huang, Xuemei Lu, Wei Chen, Xiaofang Yu*, Yu Liu* and Hao Liu*

Volume 25, Issue 1, 2025

Published on: 26 February, 2024

Page: [72 - 82] Pages: 11

DOI: 10.2174/0115680096281231240202073558

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Abstract

Background: DOCK1 has been reported to be involved in tumor progression and re-sistance.1-(2-(30-(trifluoromethyl)-[1,10-biphenyl]-4-yl)-2-oxoethyl)-5-pyrrolidinylsulfonyl2(1H)- pyridone (TBOPP) is a selective DOCK1 inhibitor; however, the role and molecular mechanisms of DOCK1 and its inhibition in breast cancer (BC) resistance remain poorly understood. Objective: This study aims toinvestigate the underlying mechanisms of DOCK1 in BC resistance.

Objective: This study aims toinvestigate the underlying mechanisms of DOCK1 in BC resistance.

Methods: DOCK1 or Twist siRNA and Twist plasmid were used to explore the function of DOCK1 in vitro experiments. A mouse xenograft model was used for in vivo experiments.

Results: In the present study, we demonstrated that DOCK1 siRNA promoted cisplatin sensitivity in BC cells. Moreover, TBOPP also enhances the therapeutic effect of cisplatin both in vitro and in vivo. Mechanistically, DOCK1 siRNA inhibited EMT. Twist 1 is one of the EMT-inducing transcription factors and is known to induce EMT. To further reveal the effect of DOCK in BC cells, we co-transfected with DOCK1 and Twist1 siRNA to BC cells and found that co-transfection with DOCK1 and Twist siRNA could not further enhance the cisplatin sensitivity of BC cells. Moreover, DOCK1 siRNA failed to reverse the effect of Twist 1 up-regulation.

Conclusion: Taken together, these results demonstrate that DOCK1 may function as a potential therapeutic target in BC and that combining cisplatin with TBOPP may provide a promising therapeutic strategy for cisplatin-resistant BC patients.

Keywords: Breast cancer, cisplatin, DOCK1, TWIST 1, epithelial-mesenchymal transition, TBOPP.

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