KIFC1 Inhibitor CW069 Induces Apoptosis and Reverses Resistance to Docetaxel in Prostate Cancer.

CW069 KIFC1 apoptosis docetaxel resistance prostate cancer

Journal

Journal of clinical medicine
ISSN: 2077-0383
Titre abrégé: J Clin Med
Pays: Switzerland
ID NLM: 101606588

Informations de publication

Date de publication:
09 Feb 2019
Historique:
received: 26 12 2018
revised: 22 01 2019
accepted: 05 02 2019
entrez: 13 2 2019
pubmed: 13 2 2019
medline: 13 2 2019
Statut: epublish

Résumé

Kinesin family member C1 (KIFC1) is a minus end-directed motor protein that plays an essential role in centrosome clustering. Previously, we reported that KIFC1 is involved in cancer progression in prostate cancer (PCa). We designed this study to assess the involvement of KIFC1 in docetaxel (DTX) resistance in PCa and examined the effect of KIFC1 on DTX resistance. We also analyzed the possible role of a KIFC1 inhibitor (CW069) in PCa. We used DTX-resistant PCa cell lines in DU145 and C4-2 cells to analyze the effect of KIFC1 on DTX resistance in PCa. Western blotting showed that KIFC1 expression was higher in the DTX-resistant cell lines than in the parental cell lines. Downregulation of KIFC1 re-sensitized the DTX-resistant cell lines to DTX treatment. CW069 treatment suppressed cell viability in both parental and DTX-resistant cell lines. DTX alone had little effect on cell viability in the DTX-resistant cells. However, the combination of DTX and CW069 significantly reduced cell viability in the DTX-resistant cells, indicating that CW069 re-sensitized the DTX-resistant cell lines to DTX treatment. These results suggest that a combination of CW069 and DTX could be a potential strategy to overcome DTX resistance.

Identifiants

DOI: 10.3390/jcm8020225 PMID: 30744126 PMC: PMC6407017
pubmed: 30744126
pii: jcm8020225
doi: 10.3390/jcm8020225
pmc: PMC6407017
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Grants-in-Aid for Scientific Research
ID : 15H04713
Organisme : Challenging Exploratory Research
ID : 26670175
Organisme : Challenging Exploratory Research
ID : 16K15247

Déclaration de conflit d'intérêts

The authors declare no conflict of interest.

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Auteurs

Yohei Sekino (Y)

Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan. yoshis413@yahoo.co.jp.
Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan. yoshis413@yahoo.co.jp.

Naohide Oue (N)

Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan. naoue@hiroshima-u.ac.jp.

Yuki Koike (Y)

Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan. b145456@hiroshima-u.ac.jp.

Yoshinori Shigematsu (Y)

Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan. nasakamoto@hiroshima-u.ac.jp.
Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan. nasakamoto@hiroshima-u.ac.jp.

Naoya Sakamoto (N)

Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan. kzsentani@hiroshima-u.ac.jp.

Kazuhiro Sentani (K)

Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan. wyasui@hiroshima-u.ac.jp.

Jun Teishima (J)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan. teishima@hiroshima-u.ac.jp.

Masaki Shiota (M)

Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. matsua@hiroshima-u.ac.jp.

Akio Matsubara (A)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan. shiota@uro.med.kyushu-u.ac.jp.

Wataru Yasui (W)

Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan. wyasui@hiroshima-u.ac.jp.

Classifications MeSH