Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Aug;35(8):1213-1221.
doi: 10.1007/s00345-016-1996-y. Epub 2017 Jan 19.

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

Chuangzhong Deng  1   2   3 , Jieping Chen  1   2   3 , Shengjie Guo  1   2   3 , Yanjun Wang  1   2   3 , Qianghua Zhou  1   2   3 , Zaishang Li  1   2   3 , Xingping Yang  4 , Xingsu Yu  2   3   5 , Zhenfeng Zhang  2   3   5 , Fangjian Zhou  1   2   3 , Hui Han  6   7   8 , Kai Yao  9   10   11
Affiliations

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

Chuangzhong Deng et al. World J Urol. 2017 Aug.

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.

Keywords: AR-V7; Bicalutamide; CX4945; Castration-resistant prostate cancer; NF-κB.

PubMed Disclaimer

References

    1. Cancer Res. 2013 Jan 15;73(2):483-9 - PubMed
    1. Nat Med. 2004 Jan;10(1):33-9 - PubMed
    1. Int J Oncol. 2003 Jun;22(6):1263-70 - PubMed
    1. J Clin Invest. 2010 Aug;120(8):2715-30 - PubMed
    1. Adv Clin Exp Med. 2014 Mar-Apr;23(2):153-8 - PubMed

MeSH terms

LinkOut - more resources