Combination of gambogic acid with cisplatin enhances the antitumor effects on cisplatin-resistant lung cancer cells by downregulating MRP2 and LRP expression

• Published in: OncoTargets and therapy 2016-01, Vol.9, p.3359-3368
• Main Authors: Zhang, Wendian, Zhou, Hechao, Yu, Ying, Li, Jingjing, Li, Haiwen, Jiang, Danxian, Chen, Zihong, Yang, Donghong, Xu, Zumin, Yu, Zhonghua
• Format: Article
• Language: English
• Subjects: Apoptosis; Breast cancer; Cancer therapies; Carboxylic acids; Care and treatment; Cell cycle; Cell growth; Chemotherapy; Cisplatin; Colorectal cancer; Dosage and administration; Drug resistance; Drug synergism; Drug therapy; Esophagus; Flow cytometry; Health aspects; Lung cancer; Medical research; Multidrug resistant organisms; Original Research; Patient outcomes; Proteins; Testing
• ISSN: 1178-6930; 1178-6930
• DOI: 10.2147/OTT.S100936

Cisplatin resistance is a main clinical problem of lung cancer therapy. Gambogic acid (GA) could prohibit the proliferation of a variety of human cancer cells. However, the effects of GA on cisplatin-resistant lung cancer are still unclear. The objective of the present study was to find out the antitumor effects of GA on cisplatin-resistant human lung cancer A549/DDP cells and further explore its underlying mechanisms. Cell Counting Kit-8 assay was used to observe the impacts of GA and/or cisplatin on the proliferation of lung cancer cells; flow cytometry was used to detect the effects of GA on cell cycle and apoptosis; Western blot was used to examine the effects of GA on the expression of lung resistance protein (LRP) and multidrug resistance-associated protein 2 (MRP2) protein in A549/DDP cells. Our results showed that GA dose- and time-dependently prohibited the proliferation and induced significant cell apoptosis in A549 and A549/DDP cells. GA also induced G0/G1 arrest in both A549/DDP and A549 cells. Moreover, GA upregulated protein expression level of cleaved caspase-3 and Bax and downregulated protein expression level of pro-caspase-9 and Bcl-2 in time- and dose-dependent way in A549/DDP cells. GA combined with cisplatin enhanced the cells apoptotic rate and reduced the cisplatin resistance index in A549/DDP cells. In addition, GA reduced the MRP2 and LRP protein expression level in A549/DDP cells. GA inhibits the proliferation, induces cell cycle arrest and apoptosis in A549/DDP cells. Combination of GA with cisplatin enhances the antitumor effects on cisplatin-resistant lung cancer cells by downregulating MRP2 and LRP expression.