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

OncoTargets and Therapy

关键词: Gambogic acid;    Cisplatin;    Drug resistance;    Lung neoplasms;    Major vault protein;    Multidrug resistance-associated protein 2;   

DOI  :  

来源: DOAJ

【 摘 要 】

Wendian Zhang,* Hechao Zhou,* Ying Yu,* Jingjing Li, Haiwen Li, Danxian Jiang, Zihong Chen, Donghong Yang, Zumin Xu, Zhonghua YuCancer Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People’s Republic of China*These authors contributed equally to this workAbstract: 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.Keywords: gambogic acid, cisplatin, drug resistance, lung cancer, lung resistance protein, multidrug resistance-associated protein 2, anti-tumor, cell cycle arrest, cell apoptosis

【 授权许可】

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