去势抵抗性前列腺癌（CRPC）多烯紫杉醇（DTX）耐受是临床治疗的瓶颈。目前认为在分裂较慢的体内前列腺肿瘤细胞中，DTX主要通过干扰微管动力阻碍AR作为转录因子的入核而发挥抑制生长作用。最近实验结果显示AR可变剪接异变体ARv7调控的异常AR通路可能会影响有丝分裂期相关基因并促进DTX耐受。我们前期工作发现：有丝分裂激酶Plk1通过磷酸化其底物促进全长AR在DTX作用下激活并能够抑制p53的功能。因此，我们推测：与全长AR不同，AR可变剪接异变体ARv7能够转录激活Plk1，Plk1一方面通过微管动力促进全长AR入核，正反馈促进增殖；另一方面，Plk1抑制p53活性从而使细胞逃逸DTX诱导的细胞凋亡，二者是导致DTX耐受的主要机制。我们拟应用多烯紫杉醇耐受前列腺癌细胞系与相应的敏感细胞系，通过Plk1阐述AR与异常的ARv7通路的差异，为克服前列腺癌DTX耐受提供新的线索。

Docetaxel(DTX) is the major drug for treating castration-resistant prostate cancer(CRPC). However, patients inevitably develop resistance to DTX and limits the efficacy of treatment. In clinical situations, DTX is believed to exert its anti-proliferative function mainly by inhibiting androgen receptor(AR) nuclear localization. Recent studies have indicated that dysregulated AR signaling mediated by AR splicing variant ARv7, can regulate mitotic genes and promote DTX resistance. Our previous work has revealed that mitotic kinase Plk1 can activate traditional AR pathway under the treatment of DTX and serve as a negative regulator of p53 by phosphorylating its substrates. Based on literature and some of our previous work, we predict that AR splicing variant ARv7 determines DTX sensitivity of prostate cancer cells. Different from traditional AR, ARv7 can transcriptionally activate Plk1. As a result, Plk1 activation will promote full-length AR nuclear localization through microtube dynamics，thus forming a positive feedback loop to promote cell proliferation. On the other hand, Plk1 will also inhibit drug-induced apoptosis by targeting p53. Consequently, these two pathways are the major reasons for DTX resistance under ARv7 activation. To test this hypothesis, we will analyze the regulation of ARv7,AR,Plk1 and p53 by comparing the DTX resistant prostate cancer cells with the parental cells. Our study aims to focus on Plk1 in order to illustrate the difference between traditional AR pathway and dysregulated ARv7 pathway, thus providing therapeutic guidance for improving the efficacy of DTX in CRPC.