Open Access

γ‑Klotho is correlated with resistance to docetaxel in castration‑resistant prostate cancer

  • Authors:
    • Kenta Onishi
    • Makito Miyake
    • Shunta Hori
    • Sayuri Onishi
    • Kota Iida
    • Yosuke Morizawa
    • Yoshihiro Tatsumi
    • Yasushi Nakai
    • Nobumichi Tanaka
    • Kiyohide Fujimoto
  • View Affiliations

  • Published online on: January 16, 2020     https://doi.org/10.3892/ol.2020.11308
  • Pages: 2306-2316
  • Copyright: © Onishi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The Klotho (KL) gene was first identified as a potent aging suppressor. The KL family currently comprises of three proteins: α‑Klotho (KLA), β‑Klotho (KLB), and γ‑Klotho (KLG). Many studies have shown that KLA and KLB participate in tumor progression or suppression, depending on the type of cancer; however, the relationship between KLG and prostate cancer has not yet been studied. Some studies have claimed that KL is correlated to sensitivity to chemotherapy. Here, we investigated the oncogenic potential of KLG in castration‑resistant prostate cancer (CRPC). Immunohistochemical analysis using prostate biopsy specimens revealed that patients with high KLG expression in primary prostate cancer tissue had a significantly poor prognosis for overall survival. In addition, the prostate‑specific antigen response rate after docetaxel (DTX) therapy in patients with high KLG expression was lower than that in patients with low KLG expression. To evaluate the potential of KLG as a therapeutic target in human prostate cancer, we generated a xenograft model of human CRPC cell line (PC‑3) in male athymic mice. The animals were randomly divided into four groups as follows: i) control group (vehicle only); ii) DTX group (intraperitoneal administration); iii) small interfering RNA targeting KLG (KLG siRNA) group (intratumoral administration); and iv) a combination group (DTX plus KLG siRNA). After 3 weeks of treatment, the tumor weight and tumor Ki‑67 labeling index were significantly lower in the KLG siRNA group and the combination group than in the control group. Sensitivity to DTX was increased upon treatment with KLG siRNA. These findings suggest that KLG expression in primary prostate cancer lesions is associated with resistance to DTX in CRPC and has potential as a diagnostic and therapeutic target for patients with CRPC.

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March 2020
Volume 19 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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APA
Onishi, K., Miyake, M., Hori, S., Onishi, S., Iida, K., Morizawa, Y. ... Fujimoto, K. (2020). γ‑Klotho is correlated with resistance to docetaxel in castration‑resistant prostate cancer. Oncology Letters, 19, 2306-2316. https://doi.org/10.3892/ol.2020.11308
MLA
Onishi, K., Miyake, M., Hori, S., Onishi, S., Iida, K., Morizawa, Y., Tatsumi, Y., Nakai, Y., Tanaka, N., Fujimoto, K."γ‑Klotho is correlated with resistance to docetaxel in castration‑resistant prostate cancer". Oncology Letters 19.3 (2020): 2306-2316.
Chicago
Onishi, K., Miyake, M., Hori, S., Onishi, S., Iida, K., Morizawa, Y., Tatsumi, Y., Nakai, Y., Tanaka, N., Fujimoto, K."γ‑Klotho is correlated with resistance to docetaxel in castration‑resistant prostate cancer". Oncology Letters 19, no. 3 (2020): 2306-2316. https://doi.org/10.3892/ol.2020.11308