title: Combination of gambogic acid with cisplatin enhances the antitumor effects on cisplatin-resistant lung cancer cells by downregulating MRP2 and LRP expression.
abstract: 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.
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China.
authors.forename: Wendian
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China.
authors.forename: Hechao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China.
authors.forename: Haiwen
authors.initials: H
authors.lastname: Li
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China.
authors.forename: Danxian
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China.
authors.forename: Zihong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China.
authors.forename: Donghong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China.
authors.forename: Zumin
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, People's Republic of China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Yu
keywords: anti-tumor; cell apoptosis; cell cycle arrest; cisplatin; drug resistance; gambogic acid; lung cancer; lung resistance protein; multidrug resistance-associated protein 2