TUBB3 Reverses Resistance to Docetaxel and Cabazitaxel in Prostate Cancer

Yohei Sekino; Xiangrui Han; Takafumi Kawaguchi; Takashi Babasaki; Keisuke Goto; Shogo Inoue; Tetsutaro Hayashi; Jun Teishima; Masaki Shiota; Wataru Yasui; Akio Matsubara

doi:10.3390/ijms20163936

International Journal of Molecular Sciences (Aug 2019)

TUBB3 Reverses Resistance to Docetaxel and Cabazitaxel in Prostate Cancer

Yohei Sekino,
Xiangrui Han,
Takafumi Kawaguchi,
Takashi Babasaki,
Keisuke Goto,
Shogo Inoue,
Tetsutaro Hayashi,
Jun Teishima,
Masaki Shiota,
Wataru Yasui,
Akio Matsubara

Affiliations

Yohei Sekino: Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Xiangrui Han: Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Takafumi Kawaguchi: Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Takashi Babasaki: Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Keisuke Goto: Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Shogo Inoue: Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Tetsutaro Hayashi: Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Jun Teishima: Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Masaki Shiota: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
Wataru Yasui: Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Akio Matsubara: Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan

DOI: https://doi.org/10.3390/ijms20163936
Journal volume & issue: Vol. 20, no. 16
p. 3936

Abstract

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Recent studies have reported that TUBB3 overexpression is involved in docetaxel (DTX) resistance in prostate cancer (PCa). The aim of this study was to clarify the role of TUBB3 in DTX and cabazitaxel (CBZ) resistance, and cross-resistance between DTX and CBZ in PCa. We analyzed the effect of TUBB3 knockdown on DTX and CBZ resistance and examined the interaction between TUBB3 and PTEN. We also investigated the role of phosphoinositide 3-kinases (PI3K) inhibitor (LY294002) in DTX and CBZ resistance. TUBB3 expression was upregulated in DTX-resistant and CBZ-resistant cells. TUBB3 knockdown re-sensitized DTX-resistant cells to DTX and CBZ-resistant cells to CBZ. Additionally, TUBB3 knockdown re-sensitized DTX-resistant cell lines to CBZ, indicating that TUBB3 mediates cross-resistance between DTX and CBZ. Knockdown of TUBB3 enhanced PTEN expression, and PTEN knockout enhanced TUBB3 expression. LY294002 suppressed TUBB3 expression in DTX-resistant and CBZ-resistant cell lines. LY294002 re-sensitized DTX-resistant cell lines to DTX and CBZ-resistant cell lines to CBZ. These results suggest that TUBB3 is involved in DTX resistance and CBZ resistance. A combination of LY294002/DTX and that of LY294002/CBZ could be potential strategies for PCa treatment.

Published in International Journal of Molecular Sciences

ISSN: 1661-6596 (Print); 1422-0067 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General); Science: Chemistry
Website: http://www.mdpi.com/journal/ijms

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