JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2017, Vol. 55 ›› Issue (9): 23-30.doi: 10.6040/j.issn.1671-7554.0.2017.145

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The therapeutic efficacy of a potent KSP inhibitor S(MeO)TLC against docetaxel-resistant prostate cancer

DONG Wei1, XING Naidong2, LÜ Jiaju1, LIU Shuai1, SUN Liang1, CAO Qingwei1, DONG Yuhao1, LIU Zhao1, DING Sentai1   

  1. 1. Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China;
    2. Department of Urology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Received:2017-02-17 Online:2017-09-10 Published:2017-09-10

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Abstract: Objective To investigate the therapeutic effect of S(MeO)TLC which targetedly inhibits KSP(Eg5)on docetaxel-resistant prostate cancer in vitro. Methods Docetaxel-resistant PC3 cells(PC3R)were developed by chronic, repeated exposure to docetaxel through gradient culture. IC50 of docetaxel-resistant cells to docetaxel was assessed with MTT assay. KSP expressions of different prostate cancer cell lines(PC3, DU145, PC3R)were examined with Western blotting. The cells were divided into control group, PC3 group and PC3R group, and the anti-proliferative activity of S(MeO)TLC was analyzed with MTT and trypan blue staining. After that, the PC3R cells were divided into 山 东 大 学 学 报 (医 学 版)55卷9期 -董伟,等.靶向抑制有丝分裂驱动蛋白治疗多西紫杉醇耐药前列腺癌的体外疗效 \=-control group and S(MeO)TLC group, and the apoptosis was investigated with Hoechst nuclear staining, flow cytometry and RT-PCR in vitro. Results The expressions of KSP in PC3, DU145, and PC3R were similar, with no statistical difference(P>0.05). There was no significant difference in IC50 between PC3R(120 nmol/L)and PC3(106 nmol/L)(P>0.05). After S(MeO)TLC treatment for 24 hours, 87.9% PC3R cells were in the mitosis phase, most of which went apoptosis after 72 hours of S(MeO)TLC treatment. Compared with the control group, PC3R group had significantly increased expressions of Caspase-3(t=13.445, P=0.000 2), Caspase-8(t=9.494, P=0.000 7), Caspase-9(t=5.198, P=0.007), PARP(t=19.097, P=0.000 04), LC3(t=22.609, P=0.000 02)and Beclin1(t=61.266, P=0.000 000 4). Conclusion The resistance of prostate cancer to docetaxel is not related to KSP expression. S(MeO)TLC, as a new KSP/Eg5 inhibitor, has shown obvious anticancer efficacy in docetaxel-resistant prostate cancer cell lines in vitro by inducing cell apoptosis, in which both endogenous and exogenous caspase-dependent apoptotic pathways play an important role, while autophagy plays a synergistic role.

Key words: Kinesin spindle protein, Docetaxel-resistant, Prostate cancer, Targeted therapy

CLC Number: 

  • R737.25
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