Sekino Yohei, Oue Naohide, Koike Yuki, Shigematsu Yoshinori, Sakamoto Naoya, Sentani Kazuhiro, Teishima Jun, Shiota Masaki, Matsubara Akio, Yasui Wataru
Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
J Clin Med. 2019 Feb 9;8(2):225. doi: 10.3390/jcm8020225.
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.
驱动蛋白家族成员C1（KIFC1）是一种向负端移动的马达蛋白，在中心体聚集过程中发挥着重要作用。此前，我们报道KIFC1参与前列腺癌（PCa）的癌症进展。我们设计了本研究来评估KIFC1在PCa多西他赛（DTX）耐药中的作用，并研究KIFC1对DTX耐药的影响。我们还分析了KIFC1抑制剂（CW069）在PCa中的可能作用。我们使用DU145和C4-2细胞中的DTX耐药PCa细胞系来分析KIFC1对PCa中DTX耐药的影响。蛋白质免疫印迹法显示，DTX耐药细胞系中KIFC1的表达高于亲本细胞系。KIFC1的下调使DTX耐药细胞系对DTX治疗重新敏感。CW069处理抑制了亲本细胞系和DTX耐药细胞系的细胞活力。单独使用DTX对DTX耐药细胞的细胞活力影响很小。然而，DTX和CW069的联合使用显著降低了DTX耐药细胞的细胞活力，表明CW069使DTX耐药细胞系对DTX治疗重新敏感。这些结果表明，CW069和DTX联合使用可能是克服DTX耐药的潜在策略。
