The Mechanisms of Yu Ping Feng San in Tracking the Cisplatin-Resistance by Regulating ATP-Binding Cassette Transporter and Glutathione S-Transferase in Lung Cancer Cells
| Autor: | Yuzhong Zheng, Jiachuan Yin, Lishan Zhong, Liyi Zeng, Xingri Zhan, Li Yafang, Karl Wah Keung Tsim, Qitian Xu, Kelvin Chan, Baomeng Wu, Ciel Xiaomei Yu, Du Yingqing, Xi Liu, Guangcai Zha, Venus Wei Xie, Elsa Wanyi Zhu, Yamiao Huang, Wei-Hui Hu, Zhenxia Zhang |
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| Rok vydání: | 2021 |
| Předmět: |
prim-o-glucosylcimifugin
0301 basic medicine RM Programmed cell death cisplatin ATP-binding cassette transporter RM1-950 anti-multidrug resistance 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Pharmacology (medical) Viability assay Original Research Pharmacology Cisplatin efflux transporters biology GSTs Glutathione 030104 developmental biology Glutathione S-transferase chemistry Apoptosis 030220 oncology & carcinogenesis Cancer research biology.protein Therapeutics. Pharmacology yu ping feng san Intracellular medicine.drug |
| Zdroj: | Frontiers in Pharmacology Frontiers in Pharmacology, Vol 12 (2021) |
| ISSN: | 1663-9812 |
| Popis: | Cisplatin is one of the first line anti-cancer drugs prescribed for treatment of solid tumors; however, the chemotherapeutic drug resistance is still a major obstacle of cisplatin in treating cancers. Yu Ping Feng San (YPFS), a well-known ancient Chinese herbal combination formula consisting of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, is prescribed as a herbal decoction to treat immune disorders in clinic. To understand the fast-onset action of YPFS as an anti-cancer drug to fight against the drug resistance of cisplatin, we provided detailed analyses of intracellular cisplatin accumulation, cell viability, and expressions and activities of ATP-binding cassette transporters and glutathione S-transferases (GSTs) in YPFS-treated lung cancer cell lines. In cultured A549 or its cisplatin-resistance A549/DDP cells, application of YPFS increased accumulation of intracellular cisplatin, resulting in lower cell viability. In parallel, the activities and expressions of ATP-binding cassette transporters and GSTs were down-regulated in the presence of YPFS. The expression of p65 subunit of NF-κB complex was reduced by treating the cultures with YPFS, leading to a high ratio of Bax/Bcl-2, i.e. increasing the rate of cell death. Prim-O-glucosylcimifugin, one of the abundant ingredients in YPFS, modulated the activity of GSTs, and then elevated cisplatin accumulation, resulting in increased cell apoptosis. The present result supports the notion of YPFS in reversing drug resistance of cisplatin in lung cancer cells by elevating of intracellular cisplatin, and the underlying mechanism may be down regulating the activities and expressions of ATP-binding cassette transporters and GSTs. |
| Databáze: | OpenAIRE |
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