Open Access

Radioresistance of chordoma cells is associated with the ATM/ATR pathway, in which RAD51 serves as an important downstream effector

  • Authors:
    • Chao Zhang
    • Bing Wang
    • Lei Li
    • Yawei Li
    • Pengzhi Li
    • Guohua Lv
  • View Affiliations

  • Published online on: July 9, 2017     https://doi.org/10.3892/etm.2017.4736
  • Pages: 2171-2179
  • Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Surgery followed by radiotherapy is the standard treatment for chordomas, which are a rare but low‑grade type of bone cancer arising from remnants of the embryonic notochord. However, disease recurrence following radiotherapy is common, most likely due to endogenous DNA repair mechanisms that promote cell survival upon radiation strikes. The ataxia telangiectasia mutated/ataxia telangiectasia mutated and Rad3 related (ATM/ATR)‑mediated pathway has a critical role in DNA repair mechanisms; however, it has rarely been investigated in chordomas. In the present study, the expression of signal molecules related to the ATM/ATR pathway in chordoma tissues and adjacent normal tissues were initially examined using immunohistochemistry and western blot analysis. Chordoma U‑CH1 and U‑CH2 cells were subsequently used to investigate cell responses to ionizing radiation and the potential protective actions mediated by the ATM/ATR pathway. Phosphorylated (p)‑ATM, p‑ATR, γ‑H2A histone family, member X (H2AX) and RAD51 were significantly upregulated in chordoma tissues relative to adjacent normal tissues (P<0.05). No significant reductions were observed in the viability of U‑CH1 and U‑CH2 cells following exposure to low‑dose (1 and 2 Gy) radiation. Radiation (1 and 2 Gy) triggered a significant upregulation in p‑ATM, γ‑H2AX and RAD51 expression in U‑CH1 cells (P<0.05), as well as a significant upregulation in p‑ATM, p‑ATR and RAD51 levels in U‑CH2 cells (P<0.05). RAD51 knockdown increased the responses of both U‑CH1 and U‑CH2 cells to 1 Gy radiation, as evidenced by the significantly decreased cell viability and increased apoptosis rate (P<0.05). Collectively, the results of the present study indicated that radioresistance of chordoma cells is associated with the ATM/ATR pathway, in which RAD51 serves as an important downstream effector. Thus, RAD51 presents a promising therapeutic target for improving the outcome of radiotherapy treatment in chordomas.

Related Articles

Journal Cover

September-2017
Volume 14 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Zhang C, Wang B, Li L, Li Y, Li P and Lv G: Radioresistance of chordoma cells is associated with the ATM/ATR pathway, in which RAD51 serves as an important downstream effector. Exp Ther Med 14: 2171-2179, 2017
APA
Zhang, C., Wang, B., Li, L., Li, Y., Li, P., & Lv, G. (2017). Radioresistance of chordoma cells is associated with the ATM/ATR pathway, in which RAD51 serves as an important downstream effector. Experimental and Therapeutic Medicine, 14, 2171-2179. https://doi.org/10.3892/etm.2017.4736
MLA
Zhang, C., Wang, B., Li, L., Li, Y., Li, P., Lv, G."Radioresistance of chordoma cells is associated with the ATM/ATR pathway, in which RAD51 serves as an important downstream effector". Experimental and Therapeutic Medicine 14.3 (2017): 2171-2179.
Chicago
Zhang, C., Wang, B., Li, L., Li, Y., Li, P., Lv, G."Radioresistance of chordoma cells is associated with the ATM/ATR pathway, in which RAD51 serves as an important downstream effector". Experimental and Therapeutic Medicine 14, no. 3 (2017): 2171-2179. https://doi.org/10.3892/etm.2017.4736