Yang Jian, Yu Yang, Liu Wei, Li Zhi, Wei Zhongqing, Jiang Rongjiang
The Second Clinical Medical College of Nanjing Medical University.
Department of Urology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Res Rep Urol. 2017 May 8;9:71-77. doi: 10.2147/RRU.S118966. eCollection 2017.
Tau, a microtubule-associated protein, has been investigated primarily in neurons. Recently, tau has been explored to be associated with increased drug resistance in various kinds of cancers. We found that the tau was expressed in prostate cancer cell lines DU145 and PC-3. We also reported that recurrent prostate cancer cells after docetaxel treatment have higher levels of microtubule-associated protein tau. In vitro, inactivation of tau by gene knockdown suppressed cell proliferation and sensitized docetaxel cytotoxicity. Also, our results demonstrated that the PI3K/Akt/mTOR pathway was upregulated in DU145 docetaxel-resistant cells compared with the DU145-naïve cells. Thus, targeting tau protein and PI3K/Akt/mTOR pathway are promising strategies to enhance docetaxel response for the treatment of prostate cancer.
tau是一种微管相关蛋白,主要在神经元中进行了研究。最近,人们发现tau与多种癌症中耐药性增加有关。我们发现tau在前列腺癌细胞系DU145和PC-3中表达。我们还报道,多西他赛治疗后的复发性前列腺癌细胞中微管相关蛋白tau水平更高。在体外,通过基因敲低使tau失活可抑制细胞增殖并增强多西他赛的细胞毒性。此外,我们的结果表明,与未接触多西他赛的DU145细胞相比,DU145多西他赛耐药细胞中的PI3K/Akt/mTOR通路被上调。因此,靶向tau蛋白和PI3K/Akt/mTOR通路是增强多西他赛治疗前列腺癌疗效的有前景的策略。