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[Effect of DNA-PKcs antisense oligodeoxynucleotides on radiosensitivity of nasopharyngeal carcinoma cell lines with
Chang-Bin Jiang1, Xiu-Fang Liu, Yu-Xiang He
1State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, P. R. China.
Background & Objective:
DNA-dependent protein kinase (DNA-PK) can repair DNA double-strand break. This study was to observe the effect of DNA-PKcs antisense oligodeoxynucleotides (ASODN) on the radiosensitivity of nasopharyngeal carcinoma (NPC) cell lines with normal or abnormal p53 functions.
Methods:
DNA-PKcs ASODN was transfected into CNE-1 and CNE-1-wtp53 cells. These cells were irradiated with 0, 0.5, 1, 2, 4, 6, or 8 Gy X-ray. Cell survival was determined by clonogenic assay. The parameters D0, Dq, and N for the single-hit multitarget model and the parameters alpha, beta, alpha/beta, and SF2 for the linear-quadratic model were calculated to evaluate the changes of radiosensitivity.
Results:
The alpha values before DNA-PKcs ASODN transfection were 0.03 in CNE-1 cells and 0.05 in CNE-1-wtp53 cells; the alpha values after transfection were 0.04 in CNE-1 cells and 0.27 in CNE-1-wtp53 cells. The SF2 before transfection were 0.73 in CNE-1 cells and 0.50 in CNE-1-wtp53 cells; the SF2 after transfection were 0.45 in CNE-1 cells and 0.21 in CNE-1-wtp53 cells. The D0 before transfection were 2.08 Gy in CNE-1 cells and 1.13 Gy in CNE-1-wtp53 cells; the D0 after transfection were 1.07 Gy in CNE-1 cells and 0.83 Gy in CNE-1-wtp53 cells. The Dq before transfection were 2.04 Gy in CNE-1 cells and 1.36 Gy in CNE-1-wtp53 cells; the Dq after transfection were 1.24 Gy in CNE-1 cells and 0.73 Gy in CNE-1-wtp53 cells. The parameter alpha of CNE-1 cells was increased after DNA-PKcs ASODN transfection, but the parameters SF2, D0, and Dq were decreased after transfection.
Conclusion:
DNA-PKcs ASODN could enhance the radiosensitivity of CNE-1 cells regardless of p53 function status.
Insights
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) antisense oligodeoxynucleotides (ASODN) enhance the radiosensitivity of nasopharyngeal carcinoma cells. This suggests ASODN can improve cancer treatment outcomes by increasing cell susceptibility to radiation therapy.
Area of Science:
- Molecular Biology
- Cancer Research
- Radiotherapy
Context:
- DNA-dependent protein kinase (DNA-PK) plays a crucial role in repairing DNA double-strand breaks.
- Nasopharyngeal carcinoma (NPC) is a type of cancer where DNA repair mechanisms influence treatment response.
- The p53 protein is a key regulator of DNA damage response and cell cycle control.
Purpose:
- To investigate the effect of DNA-PKcs antisense oligodeoxynucleotides (ASODN) on the radiosensitivity of NPC cell lines.
- To determine if p53 function status influences the efficacy of DNA-PKcs ASODN in enhancing radiosensitivity.
Summary:
- DNA-PKcs ASODN were transfected into NPC cell lines (CNE-1 and CNE-1-wtp53).
- Cells were exposed to varying doses of X-ray radiation, and cell survival was assessed using clonogenic assays.
- Radiosensitivity parameters (alpha, SF2, D0, Dq) were calculated to quantify the impact of ASODN transfection.
Impact:
- DNA-PKcs ASODN significantly increased the radiosensitivity of CNE-1 cells, as indicated by increased alpha values and decreased SF2, D0, and Dq.
- The enhancement in radiosensitivity was observed irrespective of the p53 function status of the NPC cell lines.
- These findings suggest that DNA-PKcs ASODN holds potential as an adjuvant therapy to improve the effectiveness of radiotherapy in nasopharyngeal carcinoma.
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