DNA‑PKcs phosphorylation specific inhibitor, NU7441, enhances the radiosensitivity of clinically relevant radioresistant oral squamous cell carcinoma cells

  • Authors:
    • Kentaro Ohuchi
    • Ryo Saga
    • Kazuki Hasegawa
    • Eichi Tsuruga
    • Yoichiro Hosokawa
    • Manabu Fukumoto
    • Kazuhiko Okumura
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  • Published online on: February 24, 2023     https://doi.org/10.3892/br.2023.1610
  • Article Number: 28
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Abstract

Radioresistant cancer cells lead to poor prognosis after radiotherapy. However, the mechanisms underlying cancer cell radioresistance have not been fully elucidated. Thus, the DNA damage response of clinically relevant radioresistant oral squamous cell carcinoma HSC2‑R cells, established by long‑term exposure of parental HSC2 cells to fractionated radiation, was investigated. The DNA double‑strand break (DSB) repair protein‑specific inhibitor, NU7441, which targets DNA‑dependent protein kinase catalytic subunit (DNA‑PKcs) phosphorylation, and IBR2, which targets Rad51, were administered to HSC2 and HSC2‑R cells. NU7441 administration eliminated colony formation in both cell lines under 6 Gy X‑ray irradiation, whereas IBR2 did not affect colony formation. NU7441 and IBR2 significantly enhanced 6 Gy X‑ray irradiation‑induced apoptosis in HSC2‑R cells. In HSC2‑R cells, cell cycle arrest released earlier than in HSC2 cells, and phosphorylated‑H2A histone family member X (γH2AX) expression rapidly decreased. Following NU7441 administration, γH2AX expression and the cell percentages of the G2/M phase were not decreased at 48 h after treatment in HSC2‑R cells. DNA‑PKcs has been demonstrated to regulate non‑homologous end‑joining (NHEJ) and homologous recombination (HR) repair, and the later phase of DSB repair is dominated by HR. Therefore, the results of the present study indicated that the DSB repair mechanism in HSC2‑R cells strongly depends on NHEJ and loss of HR repair function. The present study revealed a potential mechanism underlying the acquired radioresistance and therapeutic targets in radioresistant cancer cells.
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April-2023
Volume 18 Issue 4

Print ISSN: 2049-9434
Online ISSN:2049-9442

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Spandidos Publications style
Ohuchi K, Saga R, Hasegawa K, Tsuruga E, Hosokawa Y, Fukumoto M and Okumura K: DNA‑PKcs phosphorylation specific inhibitor, NU7441, enhances the radiosensitivity of clinically relevant radioresistant oral squamous cell carcinoma cells. Biomed Rep 18: 28, 2023
APA
Ohuchi, K., Saga, R., Hasegawa, K., Tsuruga, E., Hosokawa, Y., Fukumoto, M., & Okumura, K. (2023). DNA‑PKcs phosphorylation specific inhibitor, NU7441, enhances the radiosensitivity of clinically relevant radioresistant oral squamous cell carcinoma cells. Biomedical Reports, 18, 28. https://doi.org/10.3892/br.2023.1610
MLA
Ohuchi, K., Saga, R., Hasegawa, K., Tsuruga, E., Hosokawa, Y., Fukumoto, M., Okumura, K."DNA‑PKcs phosphorylation specific inhibitor, NU7441, enhances the radiosensitivity of clinically relevant radioresistant oral squamous cell carcinoma cells". Biomedical Reports 18.4 (2023): 28.
Chicago
Ohuchi, K., Saga, R., Hasegawa, K., Tsuruga, E., Hosokawa, Y., Fukumoto, M., Okumura, K."DNA‑PKcs phosphorylation specific inhibitor, NU7441, enhances the radiosensitivity of clinically relevant radioresistant oral squamous cell carcinoma cells". Biomedical Reports 18, no. 4 (2023): 28. https://doi.org/10.3892/br.2023.1610