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The natural compound gambogic acid radiosensitizes nasopharyngeal carcinoma cells under hypoxic conditions

Abstract

Aims

Hypoxia is an important factor that causes decreased local disease control as well as increased distant metastases and resistance to radiotherapy in patients with advanced nasopharyngeal carcinoma (NPC). Gambogic acid (GA), the major active ingredient of gamboge, exerts antitumor effects in vitro and in vivo. However, the molecular mechanism by which GA inhibits tumor radioresistance remains unclear. The present study aimed to investigate the radiosensitizing effects of GA on NPC and explore the underlying mechanisms.

Materials and methods

CNE-1 and CNE-2 cells exposed to hypoxia and radiation were treated with GA at different concentrations. CCK-8 assay, clonogenic assay, and flow cytometry were performed to analyze cell proliferation, colony formation, apoptosis, and cell cycle. The expression levels of hypoxia-inducible factor-1α (HIF-1α), Bcl-2, Bax, caspase-3, cyclin B1/p-cdc2 and γ-H2AX were assessed using Western blot and/or immunofluorescence analysis.

Results

Results of the CCK-8 assay, clonogenic assay, and flow cytometry showed that treatment of NPC cells with growth-suppressive concentrations of GA resulted in G2/M phase arrest and apoptosis. Western blot analysis demonstrated that GA-induced cell cycle arrest and apoptosis in CNE-2 cells was associated with upregulated expression of caspase-3 and Bax and downregulated expression of Bcl-2 and cyclin B1/p-cdc2 in hypoxia. Treatment with GA markedly decreased the expression of HIF-1α under hypoxic conditions.

Conclusions

The results of this study suggest that GA efficiently radiosensitizes NPC cells and the effect may be significant in hypoxic conditions.

Tumori 2016; 102(2): 135 - 143

Article Type: ORIGINAL RESEARCH ARTICLE

DOI:10.5301/tj.5000411

Authors

Meilin Yang, Yuehua Yang, Heqing Cui, Zhifeng Guan, Yan Yang, Hao Zhang, Xiaochen Chen, Hongchen Zhu, Xi Yang, Jing Cai, Hongyan Cheng, Xinchen Sun

Article History

Disclosures

Financial support: Our study was supported by the Natural Science Foundation of China (No. 81272504, 81472809), the Innovation Team (No. LJ201123-EH11), Jiangsu Provincial Science and Technology Projects BK2011854 (DA11), and the Six Major Talent Peak Project of Jiangsu Province. The priority academic program development of Jiangsu Higher Education Institution (JX10231801), grants from the Key Academic Discipline of Jiangsu Province “Medical Aspects of Specific Environments,” and “333” Project of Jiangsu Province BRA2012210 (RS12) funded our study.
Conflict of interest: The authors declare that there are no known conflicts of interest associated with this publication.

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Authors

Affiliations

  • Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province - China
  • Department of Radiotherapy, Second People’s Hospital of Lianyungang, Lianyungang Hospital Affiliated to Bengbu Medical College, Lianyungang, Jiangsu Province - China
  • Department of Radiotherapy, The Affiliated Tumor Hospital of Nantong University, Nantong, Jiangsu Province - China
  • Department of Synthetic Internal Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province - China
  • Meilin Yang, Yuehua Yang and Heqing Cui contributed equally to this work.

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