XRCC2 Promotes colorectal cancer cell growth, regulates cell cycle progression, and apoptosis

  • K. X
  • X. S
  • Z. C
 et al. 
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Abstract

X-ray repair complementing defective repair in Chinese hamster cells 2 (XRCC2) and poly(ADP-ribose) polymerase 1 (PARP1) both play important roles in homologous recombination DNA repair. According to the theory of synthetic lethality, XRCC2-deficient cells are more sensitive to PARP1 inhibitors compared to XRCC2-expressing cells. We investigated XRCC2 expression and function in colorectal cancer (CRC), and the characteristics of sensitivity to PARP1 inhibitor in CRC cells with different XRCC2 levels.We enrolled 153 patients with CRC who had undergone surgery in this study. XRCC2 expression was assessed using immunohistochemistry. Stable CRC SW480 cell lines with low or high XRCC2 expression were constructed. Following treatment with the PARP1 inhibitor olaparib, the viability of cells with different XRCC2 levels was determined; cell cycle distribution and apoptosis were analyzed using flow cytometry. B-cell lymphoma-2 (Bcl-2) protein expression was measured by Western blotting.The positive rates of XRCC2 in primary CRC tissue were significantly higher than that in the matched adjacent noncancerous tissue, and XRCC2 expression status in primary CRC was related to tumor site, Dukes' stage, and tumor-nodes-metastasis (TNM) stage. XRCC2 overexpression inhibited CRC cell apoptosis and promoted proliferation by enriching cells in the G0/G1 phase. Moreover, olaparib suppressed proliferation, and olaparib sensitivity in CRC cells with high XRCC2 expression was greater.High XRCC2 expression promotes CRC cell proliferation and enriches cells in the G0/G1 phase but inhibits apoptosis. High XRCC2 expression cells are more sensitive to olaparib, which inhibits their viability.

Author-supplied keywords

  • Adult
  • Apoptosis
  • Blotting
  • Cell Cycle
  • Cell Growth Processes
  • Cell Line
  • Colorectal Neoplasms
  • DNA-Binding Proteins
  • Disease Progression
  • Female
  • Flow Cytometry
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm
  • Neoplastic
  • RNA
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Tumor
  • Western
  • Western blotting
  • X ray repair complementing defective repair in Chi
  • adult
  • apoptosis
  • article
  • biosynthesis
  • cancer growth
  • cancer staging
  • cell cycle G0 phase
  • cell cycle G1 phase
  • cell cycle progression
  • cell proliferation
  • cell viability
  • cellular distribution
  • colorectal cancer
  • colorectal cancer cell line
  • controlled study
  • dose time effect relation
  • female
  • flow cytometry
  • gene overexpression
  • genetics
  • human
  • human cell
  • human tissue
  • immunohistochemistry
  • major clinical study
  • male
  • metabolism
  • middle aged
  • olaparib
  • pathology
  • protein
  • protein bcl 2
  • protein expression
  • protein function
  • unclassified drug
  • upregulation

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Authors

  • Xu K.

  • Song X.

  • Chen Z.

  • Qin C.

  • He Y.

  • Zhan W.

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