title: Reversal effect and mechanism ofGinkgo bilobaexocarp extracts in multidrug resistance of mice S180 tumor cells.
abstract: The aim of the present study was to investigate the reversal effect and its related mechanism ofGinkgo bilobaexocarp extracts (GBEEs) in obtained multidrug resistance (MDR) of mice S180 tumor cellsin vitroandin vivo. In order to simulate the clinical PFC [cis-dichlorodiamineplatinum, cisplatin (DDP) + fluorouracil (FU), FU+cyclophosphamide and cyclophosphamide] scheme, a gradually increasing dose was administered in a phased induction in order to induce S180 cellsin vivoand to make them obtain multidrug resistance. The resultsin vitrodemonstrated that GBEE could significantly increase the IC50of DDP on S180 MDR cells, increase the accumulation of Adriamycin (ADR) and rhodamine 123 (Rho 123), and reduce the efflux of Rho 123 of S180 MDR cells. The results from thein vivotreatment with a combination of GBEE and DDP to S180 MDR ascites tumor in mice demonstrated that each dose of GBEE could effectively reverse the drug-resistance of S180 MDR cells to DDP in order to extend the survival time of mice with ascite tumors and inhibit tumor growth in solid tumor mice. In addition, GBEE effectively inhibited the expression of MDR-1 mRNA and multidrug resistance-associated protein-1 mRNA in S180 MDR cells of ascites tumor in mice and improved the expression levels of cytokines, including interleukin (IL)-3, IL-18 and interferon-γ in the blood serum of S180 MDR tumor-bearing mice. The present study showed that the mechanism of GBEE reversal of MDR may be associated with the inhibition of the functional activity of P-glycoprotein, the downregulation of drug resistance related gene expression of S180 MDR cells and the improvement of the production of related serum cytokines of S180 MDR tumor mice.
authors.affiliation: Department of Pharmacology, Medical College of Yangzhou University, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Bi-Yuan
authors.initials: BY
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Medical College of Yangzhou University, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Yun-Hao
authors.initials: YH
authors.lastname: Gu
authors.affiliation: Department of Pharmacology, Medical College of Yangzhou University, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Chen-Jie
authors.initials: CJ
authors.lastname: Cao
authors.affiliation: Department of Pharmacology, Medical College of Yangzhou University, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Medical College of Yangzhou University, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Han
authors.affiliation: Department of Pharmacology, Medical College of Yangzhou University, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Ying-Chao
authors.initials: YC
authors.lastname: Tang
authors.affiliation: Department of Pharmacology, Medical College of Yangzhou University, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Hua-Sheng
authors.initials: HS
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Medical College of Yangzhou University, Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu 225001, P.R. China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Xu
keywords: Ginkgo biloba exocarp extracts; cytokines; drug-resistant genes; multidrug resistance; p-glycoprotein