YEONG-SHIAU PUCHAO-YUAN HUANGWu, Hung-LinHung-LinWuWu, Jyun-HongJyun-HongWuSu, Ying-FangYing-FangSuYu, Chang-Tze RickyChang-Tze RickyYuLu, Chi-YuChi-YuLuWu, Wen-JengWen-JengWuHuang, Shu-PinShu-PinHuangHuang, Ying-TangYing-TangHuangHour, Tzyh-ChyuanTzyh-ChyuanHour2024-03-132024-03-132024-011607551Xhttps://scholars.lib.ntu.edu.tw/handle/123456789/640814Docetaxel-based chemotherapy has generally been considered as one of the effective treatments for castration-resistant prostate cancer (PCa). However, clinical treatment with docetaxel often encounters a number of undesirable effects, including drug resistance. Tubulin isoforms have been previously examined for their resistance to docetaxel in many cancers, but their real mechanisms remained unclear. In this study, a series of docetaxel-resistant PC/DX cell sublines were established by chronically exposing PC3 to progressively increased concentrations of docetaxel. Western blotting results showed significantly higher expression of acetyl-tubulin, α-tubulin, β-tubulin, γ-tubulin, and βIII-tubulin in PC/DX25 than in parental PC3 cells. PC/DX25 with greater resistance to docetaxel had higher levels of acetyl-tubulin and mitotic centromere-associated kinesin (MCAK) than PC3 cells. This study found that docetaxel induced the expression of acetyl-tubulin and MCAK in PC3 cells at a dose- and time-dependent manner. Both mRNA and protein levels of histone deacetylase 6 (HDAC6) were significantly decreased in PC/DX25 compared with PC3 cells. PC3 increased the resistance to docetaxel by HDAC6 knockdown and Tubastatin A (HDAC6 inhibitor). Conversely, PC/DX25 reversed the sensitivity to docetaxel by MCAK knockdown. Notably, flow cytometry analysis revealed that MCAK knockdown induced significantly sub G1 fraction in PC/DX cells. Overexpression of polo-like kinase-1 increased the cell survival rate and resistance to docetaxel in PC3 cells. Moreover, epidermal growth factor receptor (EGFR) activation induced the upregulation of acetyl-tubulin in docetaxel-resistant PCa cells. These findings demonstrated that the EGFR-mediated upregulated expression of acetyl-tubulin played an important role in docetaxel-resistant PCa.enHDAC6; acetyl-tubulin; docetaxel; drug resistance; prostate cancer[SDGs]SDG3journal article10.1002/kjm2.12766379167402-s2.0-85175815459https://api.elsevier.com/content/abstract/scopus_id/85175815459