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Targeting DNA-PKcs increased anticancer drug sensitivity by suppressing DNA damage repair in osteosarcoma cell line

Xin Li1, Jiguang Tian2, Qiyu Bo3

  • 1Department of Orthopedics, Qilu Hospital, Shandong University, Shandong, China.

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
|June 26, 2015
PubMed

Insights

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is expressed in osteosarcoma cells and aids chemotherapy resistance. Inhibiting DNA-PKcs increases sensitivity to drugs like cisplatin and etoposide by enhancing apoptosis and cell cycle arrest.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Chemotherapy resistance, often due to DNA damage repair, drives cancer metastasis and recurrence.
  • DNA-dependent protein kinase (DNA-PK) is crucial in the non-homologous end joining (NHEJ) DNA repair pathway.

Purpose of the Study:

  • To investigate the expression of DNA-PK catalytic subunit (DNA-PKcs) in the osteosarcoma MG63 cell line.
  • To determine the role of DNA-PKcs in chemotherapy drug resistance mediated by DNA repair.

Main Methods:

  • Assessed DNA-PKcs expression in osteosarcoma MG63 cells.
  • Examined the effect of cisplatin (DDP) and etoposide (VP16) on pDNA-PKcs(T2609) levels.
  • Investigated the impact of DNA-PKcs down-regulation on cellular response to DDP and VP16, including apoptosis and cell cycle progression.

Main Results:

  • DNA-PKcs was detected in the osteosarcoma MG63 cell line.
  • Treatment with DDP and VP16 increased the expression of pDNA-PKcs(T2609).
  • Reducing DNA-PKcs levels sensitized MG63 cells to DDP and VP16, leading to increased apoptosis and G1 phase cell cycle arrest.

Conclusions:

  • DNA-PKcs is expressed in osteosarcoma MG63 cells and plays a role in DNA damage repair.
  • DNA-PKcs expression is associated with resistance to DNA-damaging chemotherapy agents.
  • Targeting DNA-PKcs may enhance the efficacy of chemotherapy in osteosarcoma by overcoming drug resistance.
Keywords:
DNA damage repairDNA-PKcsDrug resistanceOsteosarcoma

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