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TUBB3 Reverses Resistance to Docetaxel and Cabazitaxel in Prostate Cancer

1
Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
2
Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan
3
Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(16), 3936; https://doi.org/10.3390/ijms20163936
Received: 22 July 2019 / Revised: 3 August 2019 / Accepted: 5 August 2019 / Published: 13 August 2019
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Abstract

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. View Full-Text
Keywords: prostate cancer; TUBB3; PTEN; docetaxel; cabazitaxel; cross-resistance; LY294002 prostate cancer; TUBB3; PTEN; docetaxel; cabazitaxel; cross-resistance; LY294002
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    Doi: 10.5281/zenodo.3345555
    Description: Supplementary Table 1. Clinicopathological characteristics of the patients with prostate cancer. Supplementary figure 1. TUBB3 is overexpressed in docetaxel (DTX) resistant cell lines and cabazitaxel (CBZ) resistant cell lines. (A) The results of qRT-PCR for the expression of TUBB3 in parental and DTX resistant cell lines in C4-2 and DU145 cells. The results are expressed as the mean ± S.D. of triplicate measurements. (B) The results of qRT-PCR for the expression of TUBB3 in parental and CBZ resistant cell lines in LNCaP and 22Rv-1 cells. The results are expressed as the mean ± S.D. of triplicate measurements.
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Sekino, Y.; Han, X.; Kawaguchi, T.; Babasaki, T.; Goto, K.; Inoue, S.; Hayashi, T.; Teishima, J.; Shiota, M.; Yasui, W.; Matsubara, A. TUBB3 Reverses Resistance to Docetaxel and Cabazitaxel in Prostate Cancer. Int. J. Mol. Sci. 2019, 20, 3936.

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