title: [Employing DNA Damage Response Inhibitors to Enhance Chemosensitivity of Ovarian Carcinoma Cells].
abstract: OBJECTIVE
  To assess the sensitisation effects of DDR inhibitors combined with conventional chemotherapeutics agents (cisplatin et al) in a drug-resistant ovarian cancer cell line(OVCAR-8).
  
  
  METHODS
  Inhibitors of DDR regulators with cisplatin were applied to challenge OVCAR-8, and evaluated the DNA damage response (DDR) and cytotoxic effects of different combination of chemicals. Inhibition of proliferation to OVCAR-8 of different drugs was evaluated by MTT assay. The activation of phosphorylation of histone family 2A variant (yH2AX) and p53 binding protein 1 (53BP1) in OVCAR-8 were evaluated by immunofluorescence to observe their ability of recruitment and forming foci at DNA damage site.
  
  
  RESULTS
  We observed that combined treatment of ataxia-telangiectasia mutated (ATM)/ATM and Rad 3-related (ATR) inhibitor and cisplatin can suppress the activation of damage repair mechanisms and weakened the proliferative activity of OVCAR-8 cells (P<0. 01) ; ATR pathway was suppressed and the signal of γH2AX weakened and cell survival rate significantly reduced when combination therapy of HU and Wortmannin (P < 0.05); poly ADP-ribose polymerase (PARP) inhibitor could not enhance chemosensitivity in OVCAR-8 cells when combined with cisplatin (P > 0.05).
  
  
  CONCLUSIONS
  We substantiated that appropriate inhibitors of DNA damage response may have a potential to improve the anti-tumor effect of conventional chemotherapy drugs and prevent drug resistances.
authors.forename: Si-yuan
authors.initials: SY
authors.lastname: Cai
authors.forename: Zi-zhi
authors.initials: ZZ
authors.lastname: Tang
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.forename: Xiao-jun
authors.initials: XJ
authors.lastname: Wang
authors.forename: Jiang-yan
authors.initials: JY
authors.lastname: Lou
authors.forename: Cong
authors.initials: C
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D064007:Ataxia Telangiectasia Mutated Proteins / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D019008:Drug Resistance, Neoplasm; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000473:pathology*; D010766:Phosphorylation; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology*; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D064007:Ataxia Telangiectasia Mutated Proteins; D002945:Cisplatin