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Oncol Lett. 2017 Jan;13(1):37-44. doi: 10.3892/ol.2016.5435. Epub 2016 Nov 25.

Role of gambogic acid and NaI131 in A549/DDP cells.

Author information

1
Department of Pneumology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
2
Department of Clinical Medicine, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
3
Department of Nuclear Medicine, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
4
Department of Central Laboratory, Wuxi Maternity and Child Health Care Hospital, Affiliated to Nanjing Medical University, Wuxi, Jiangsu 210004, P.R. China.

Abstract

Resistance to platinum in tumor tissue is a considerable barrier against effective lung cancer treatment. Radionuclide therapy is the primary adjuvant treatment, however, the toxic side effects limit its dosage in the clinical setting. Therefore, the present study aimed to determine whether an NaI131 radiosensitizer could help reduce the toxic side effects of radionuclide therapy. In vitro experiments were conducted to determine whether NaI131 can inhibit platinum resistance in A549/DDP cells, which are cisplatin-resistant non-small cell lung cancer cells, and whether gambogic acid (GA) is an effective NaI131 radiosensitizer. Cell proliferation following drug intervention was analyzed using MTT and isobolographic analysis. Apoptosis was assessed by flow cytometry. In addition, the mechanisms of drug intervention were analyzed by measuring the expression of P-glycoprotein (P-gP), B cell lymphoma 2 (Bcl-2), Bcl2-associated X protein (Bax) and P53 using western blot analysis and immunocytochemistry. According to isobolographic analysis, a low concentration of NaI131 combined with GA had a synergistic effect on the inhibition of A549/DDP cell proliferation, which was consistent with an increased rate of apoptosis. Furthermore, the overexpression of Bax, and the downregulation of P-gP, P53 and Bcl-2 observed demonstrated the potential mechanism(s) of NaI131 and GA intervention. NaI131 may induce apoptosis in A549/DDP cells by regulating apoptosis-related proteins. A low concentration combination of NaI131 and GA was able to significantly inhibit A549/DDP cell proliferation and induce cell apoptosis. Thus, the two drugs appear to have a synergistic effect on apoptosis of A549/DDP cells.

KEYWORDS:

A549/DDP cells; NaI131; cell apoptosis; gambogic acid

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