title: Silencing of CDC20 suppresses metastatic castration-resistant prostate cancer growth and enhances chemosensitivity to docetaxel.
abstract: The role of cell division cycle 20 (CDC20) was investigated in chemoresistance to decetaxel and the underlying mechanisms in metastatic castration-resistant prostate cancer (mCRPC). MTT assays were performed to determine effects of siRNA-mediated CDC20 knockdown on cell proliferation and anticancer activity of docetaxel. Western blot analyses were conducted to detect changes of Akt and Wnt signaling. Furthermore, in vivo growth of PCa was examined in nude mice treated with siCDC20 or docetaxel alone or in combination. CDC20 was overexpressed in mCRPC cells. Knockdown of CDC20 suppressed cell proliferation and enhanced anticancer effect of docetaxel with IC50 reducing from 0.358 to 0.188 µg/ml in PC3 cells and 0.307 to 0.162 µg/ml in DU145 cells (P<0.01). While no change of Akt signaling was observed, inhibition of Wnt/β-catenin signaling was detected upon CDC20 silencing. Xenograft tumor growth was significantly reduced in nude mice by CDC20 inhibition. The additional treatment of siCDC20 achieved better anticancer effects than that of docetaxel alone. Silencing of CDC20 may be a new strategy to improve chemosensitization to docetaxel in mCRPC.
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Urology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Dejuan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Si-Tu
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Minhua
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Shubin
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Jianguang
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D064199:Cdc20 Proteins / Q000037:antagonists & inhibitors*; D049109:Cell Proliferation; D000077143:Docetaxel; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043823:Taxoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D064199:Cdc20 Proteins; D012333:RNA, Messenger; D043823:Taxoids; C577488:CDC20 protein, human; D000077143:Docetaxel