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

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. Y u P ing F eng S an (YPFS), a well-known ancient Chinese herbal combination formula consisting of...

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Published in:	Frontiers in pharmacology Vol. 12; p. 678126
Main Authors:	Du, Yingqing, Zheng, Yuzhong, Yu, Ciel Xiaomei, Zhong, Lishan, Li, Yafang, Wu, Baomeng, Hu, Weihui, Zhu, Elsa Wanyi, Xie, Venus Wei, Xu, Qitian, Zhan, Xingri, Huang, Yamiao, Zeng, Liyi, Zhang, Zhenxia, Liu, Xi, Yin, Jiachuan, Zha, Guangcai, Chan, Kelvin, Tsim, Karl Wah Keung
Format:	Journal Article
Language:	English
Published:	Frontiers Media S.A 28-05-2021
Subjects:	anti-multidrug resistance cisplatin efflux transporters GSTs Pharmacology prim-o-glucosylcimifugin yu ping feng san
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Summary:	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. Y u P ing F eng S an (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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology Edited by: Jun Peng, Fujian University of Traditional Chinese Medicine, China Xiudao Song, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, China Reviewed by: Huang-Quan Lin, The Chinese University of Hong Kong, China
ISSN:	1663-9812 1663-9812
DOI:	10.3389/fphar.2021.678126