title: Biological effects of novel "combi-targeting" molecule and its effect on DNA repair pathway in hormone-refractory prostate cancer.
abstract: OBJECTIVE
  This study aimed to investigate the biological effects of "combi-targeting" JDF12 and its effect on the DNA repair pathway in hormone-refractory prostate cancer (HRPC).
  
  
  METHODS
  HRPC cell lines (PC3 cells and VCap cells) were treated with JDF12 at different concentrations, and SRB method was employed to detect the proliferation of HRPC cells; Annexin V-FITC kit was used to detect the apoptosis of PC3 cells; Alkaline comet assay was performed to detect DNA damage; Western blot assay was done to detect the expressions of autophosphorylated EGFR, XRCC1 and ERCC1 (later two are proteins in DNA repair pathway); the anti-tumor effect was evaluated in nude mice inoculated with PC3 cells.
  
  
  RESULTS
  JDF12 could inhibit the proliferation of PC3 cells and VCap cells in a concentration dependent manner (IC50: 14.04 ± 1.22 for PC3 and 15.57 ± 1.13 for VCap) and significantly increase the apoptotic cells as compared to those treated with mitozolomide or iressa alone. In PC3 cells, JDF12 induced DNA damage and also inhibited the expressions of phosphorylated EGFR, XRCC1 and ERCC1 in a concentration dependent manner. Moreover, JDF12 markedly inhibited tumor growth in nude mice.
  
  
  CONCLUSIONS
  The novel "combi-targeting" JDF12 may exert more potent anti-proliferative effect as compared to mitozolomide or iressa alone, and the inhibitory effect on the EGFR signaling pathway and down-regulated XRCC1 and ERCC1 expressions may be ascribed to the JDF12 induced DNA damage.
authors.affiliation: Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510630, Guangdong, China.
authors.forename: Youqiang
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510630, Guangdong, China.
authors.forename: Jieying
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510630, Guangdong, China.
authors.forename: Tengcheng
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510630, Guangdong, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Wuhan Denuomei Biological Pharmaceutical Co., Ltd. Wuhan 430000, Hubei, China.
authors.forename: Qiyu
authors.initials: Q
authors.lastname: Qiu
authors.affiliation: Wuhan Denuomei Biological Pharmaceutical Co., Ltd. Wuhan 430000, Hubei, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Quan
authors.affiliation: Department of Urology, Affiliated Hospital of Guilin Medical College Guilin 541004, Guangxi, China.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510630, Guangdong, China ; Guangdong Provincial Key Laboratory of Liver Disease, The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510630, Guangdong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
keywords: Combi-targeting molecule; DNA repair pathway; JDF12; hormone-refractory prostate cancer