title: Combined olaparib and oxaliplatin inhibits tumor proliferation and induces G2/M arrest and γ-H2AX foci formation in colorectal cancer.
abstract: BACKGROUND
  Poly (ADP-ribose) polymerase 1 (PARP1) has an important role in homologous recombination repair. The purpose of this study was to investigate the effect of PARP1 inhibitor on oxaliplatin treatment for colorectal cancer (CRC).
  
  
  METHODS
  A cell counting kit-8 assay was used to determine the sensitivity of CRC cells to olaparib and/or oxaliplatin. The gene and protein expressions of PARP1 and the gamma histone variant H2AX (γH2AX) were measured by real-time quantitative polymerase chain reaction and western blotting, respectively. The γH2AX foci formation assay was used to investigate the influence of treatments on cells. Flow cytometry was used to examine the changes in cell cycle distribution. Finally, we investigated the combination of olaparib and oxaliplatin in the CRC tumor model.
  
  
  RESULTS
  Olaparib changed the expression of γH2AX and PARP1, and increased the sensitivity of CRC cells to oxaliplatin. The γH2AX foci assay showed that olaparib did not induce double-strand breaks (DSBs) alone, but it enhanced the induction of DSBs by oxaliplatin. The flow cytometry results showed that cells exposed to combination treatment had more G2/M-phase cells than control. Additionally, tumor xenograft studies suggested that combined treatment inhibited the growth of CRC.
  
  
  CONCLUSIONS
  CRC cells are sensitized to combined treatment with olaparib and oxaliplatin, and this could be a promising strategy for clinical chemotherapy in CRC.
authors.affiliation: Endoscopy Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People's Republic of China.
authors.forename: Kaiwu
authors.initials: K
authors.lastname: Xu
authors.affiliation: Gastrointestinal Surgery Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People's Republic of China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Endoscopy Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Gastrointestinal Surgery Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People's Republic of China.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Qin
authors.affiliation: Gastrointestinal Surgery Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People's Republic of China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: He
authors.affiliation: Gastrointestinal Surgery Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People's Republic of China.
authors.forename: Xinming
authors.initials: X
authors.lastname: Song
keywords: chemosensitization; colorectal cancer; olaparib; oxaliplatin