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Article

GSTM3 reverses the resistance of hepatoma cells to radiation by regulating the expression of cell cycle/apoptosis‑related molecules

  • Authors:
    • Ying Sun
    • Yu Wang
    • Yufeng Yin
    • Xianghua Chen
    • Zhijun Sun
  • View Affiliations / Copyright

    Affiliations: Department of Internal Medicine, Shandong Medical College, Jinan, Shandong 250002, P.R. China, Department of Gastroenterology, People's Hospital of Rizhao, Rizhao, Shandong 276825, P.R. China, The Health Education and Training Center of Shandong Province, Jinan, Shandong 250014, P.R. China
  • Pages: 1435-1440
    |
    Published online on: July 17, 2014
       https://doi.org/10.3892/ol.2014.2358
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Abstract

Radiotherapy (RT) is a major modality of hepatoma treatment. However, liver tumors often acquire radioresistance, which contributes to RT failure. The exact mechanisms of the radioresistance in hepatoma cells are largely unknown. Glutathione S‑transferase M3 (GSTM3) is a phase II transferase, however, recent studies have suggested that GSTM3 is a potential tumor suppressor. The purpose of the present study was to investigate the role of GSTM3 in reversing radioresistance, and to explore the molecular mechanism of this in the human radiation‑resistant PRF/PLC/5R hepatocellular carcinoma (HCC) cell line. The radioresistant PLC/PRF/5R cells were used as cell model, and were derived from PLC/PRF/5 parental cells using fractionated irradiation. The radiosensitivity of the cells was tested by clonogenic assay and flow cytometry analyses. The expression of B‑cell chronic lymphocytic leukemia/lymphoma 2 (Bcl‑2), Bax, p21, p27 and p53 was analyzed by quantitative polymerase chain reaction and immunoblotting with or without radiation. The results showed that the expression levels of GSTM3 were significantly lower in the PLC/PRF/5R cells than in the PLC/PRF/5 parental cells. GSTM3 overexpression sensitized the PLC/PRF/5R cells to radiation mainly though induction of apoptosis. According to the evidence from Annexin‑V/PI staining, it markedly increased the percentage of apoptotic PRF/PLC/5R cells. The clonogenic assay indicated that GSTM3 significantly decreased the RT survival fraction in PRF/PLC/5R cells. Furthermore, GSTM3 increased the expression of cell cycle‑ and apoptosis‑related genes (Bcl‑2, Bax, p21, p27 and p53) in PRF/PLC/5R cells with irradiation. These findings suggest that GSTM3 plays an pivotal role in reversing the radioresistance of HCC and may be a potential target for sensitizing HCC cells to RT. The underlying mechanisms may be linked to the cell cycle arrest and apoptosis facilitation.
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Copy and paste a formatted citation
Spandidos Publications style
Sun Y, Wang Y, Yin Y, Chen X and Sun Z: GSTM3 reverses the resistance of hepatoma cells to radiation by regulating the expression of cell cycle/apoptosis‑related molecules. Oncol Lett 8: 1435-1440, 2014.
APA
Sun, Y., Wang, Y., Yin, Y., Chen, X., & Sun, Z. (2014). GSTM3 reverses the resistance of hepatoma cells to radiation by regulating the expression of cell cycle/apoptosis‑related molecules. Oncology Letters, 8, 1435-1440. https://doi.org/10.3892/ol.2014.2358
MLA
Sun, Y., Wang, Y., Yin, Y., Chen, X., Sun, Z."GSTM3 reverses the resistance of hepatoma cells to radiation by regulating the expression of cell cycle/apoptosis‑related molecules". Oncology Letters 8.4 (2014): 1435-1440.
Chicago
Sun, Y., Wang, Y., Yin, Y., Chen, X., Sun, Z."GSTM3 reverses the resistance of hepatoma cells to radiation by regulating the expression of cell cycle/apoptosis‑related molecules". Oncology Letters 8, no. 4 (2014): 1435-1440. https://doi.org/10.3892/ol.2014.2358
Copy and paste a formatted citation
x
Spandidos Publications style
Sun Y, Wang Y, Yin Y, Chen X and Sun Z: GSTM3 reverses the resistance of hepatoma cells to radiation by regulating the expression of cell cycle/apoptosis‑related molecules. Oncol Lett 8: 1435-1440, 2014.
APA
Sun, Y., Wang, Y., Yin, Y., Chen, X., & Sun, Z. (2014). GSTM3 reverses the resistance of hepatoma cells to radiation by regulating the expression of cell cycle/apoptosis‑related molecules. Oncology Letters, 8, 1435-1440. https://doi.org/10.3892/ol.2014.2358
MLA
Sun, Y., Wang, Y., Yin, Y., Chen, X., Sun, Z."GSTM3 reverses the resistance of hepatoma cells to radiation by regulating the expression of cell cycle/apoptosis‑related molecules". Oncology Letters 8.4 (2014): 1435-1440.
Chicago
Sun, Y., Wang, Y., Yin, Y., Chen, X., Sun, Z."GSTM3 reverses the resistance of hepatoma cells to radiation by regulating the expression of cell cycle/apoptosis‑related molecules". Oncology Letters 8, no. 4 (2014): 1435-1440. https://doi.org/10.3892/ol.2014.2358
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