title: Role of gambogic acid and NaI131in A549/DDP cells.
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 NaI131radiosensitizer could help reduce the toxic side effects of radionuclide therapy.In vitroexperiments were conducted to determine whether NaI131can 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 NaI131radiosensitizer. 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 NaI131combined 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 NaI131and GA intervention. NaI131may induce apoptosis in A549/DDP cells by regulating apoptosis-related proteins. A low concentration combination of NaI131and 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.
authors.affiliation: Department of Pneumology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Pneumology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Clinical Medicine, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pneumology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Nuclear Medicine, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Nuclear Medicine, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Central Laboratory, Wuxi Maternity and Child Health Care Hospital, Affiliated to Nanjing Medical University, Wuxi, Jiangsu 210004, P.R. China.
authors.forename: Daozhen
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Pneumology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pneumology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pneumology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
keywords: A549/DDP cells; NaI131; cell apoptosis; gambogic acid