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Erschienen in: World Journal of Urology 8/2017

19.01.2017 | Original Article

CX4945 suppresses the growth of castration-resistant prostate cancer cells by reducing AR-V7 expression

verfasst von: Chuangzhong Deng, Jieping Chen, Shengjie Guo, Yanjun Wang, Qianghua Zhou, Zaishang Li, Xingping Yang, Xingsu Yu, Zhenfeng Zhang, Fangjian Zhou, Hui Han, Kai Yao

Erschienen in: World Journal of Urology | Ausgabe 8/2017

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Abstract

Purpose

The aberrant expression of casein kinase 2 (CK2) has been reported to be involved in the tumorigenesis and progression of prostate cancer. The inhibition of CK2 activity represses androgen-dependent prostate cancer cells by attenuating the androgen receptor (AR) signaling pathway. In this study, we examined the effect of CK2 inhibition in castration-resistant prostate cancer (CRPC) cells, in which AR variants (ARVs) play a predominant role.

Methods

A newly synthetic CK2 selective inhibitor CX4945 was utilized to study the effect of CK2 inhibition in CRPC cells by CCK8 assay and colony formation assay. Protein and mRNA levels of full-length AR (AR-FL) and AR-V7 were determined by qPCR and western blot, respectively. The nuclear translocation of p50 and p65 was assessed to reflect the activity of the NF-κB pathway.

Results

CX4945 reduced the proliferation of CRPC cells in a dose-dependent and time-dependent manner. AR-V7 rather than AR-FL was downregulated by CX4945 in both the mRNA and protein level. Furthermore, CX4945 could restore the sensitivity of CRPC cells to bicalutamide. The analysis of possible mechanisms demonstrated that the inhibition of CK2 diminished the phosphorylation of p65 at ser529 and thus attenuated the activity of the NF-κB pathway.

Conclusion

The inhibition of CK2 by CX4945 can repress the viability of CRPC cells and restore their sensitivity to anti-androgen therapy by suppressing AR-V7. This finding presents a potential option for the treatment of prostate cancer, especially CRPC.
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Metadaten
Titel
CX4945 suppresses the growth of castration-resistant prostate cancer cells by reducing AR-V7 expression
verfasst von
Chuangzhong Deng
Jieping Chen
Shengjie Guo
Yanjun Wang
Qianghua Zhou
Zaishang Li
Xingping Yang
Xingsu Yu
Zhenfeng Zhang
Fangjian Zhou
Hui Han
Kai Yao
Publikationsdatum
19.01.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
World Journal of Urology / Ausgabe 8/2017
Print ISSN: 0724-4983
Elektronische ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-016-1996-y

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