Zuo Jin Wan reverses P-gp-mediated drug-resistance by inhibiting activation of the PI3K/Akt/NF-κB pathway

BMC Complementary and Alternative Medicine

Research Article

Yu Feng¹  Li-Hong Zhou²  Wen-Hai Wang²  Hua Sui²  Xiao-Ling Fu²  Hui-Rong Zhu²  Bao-Hui Jin²  Qi Li²  Xuan Liu²  Zhi-Fen Han²  Feng-Gang Hou³  Jian-Lin Ren³  Shu-Fang Pan⁴  Xiao-Lan Shi⁴ 

[1] Department of General Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China;Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China;Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, 200071, Shanghai, China;Interventional Cancer Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, 201203, Shanghai, China;

关键词: Drug-resistance;    Akt;    NF-κB;    ABCB1;    ZJW;   

DOI  :  10.1186/1472-6882-14-279

 received in 2014-01-11, accepted in 2014-07-14,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundZuo-Jin-Wan (ZJW), a traditional Chinese medicine formula, has been identified to be effective against drug resistance in cancer. In the present study, we investigated the effect of ZJW on acquired oxaliplatin-resistant and the PI3K/Akt/NF-κB pathway in vitro.MethodsWe tested the dose–response relationship of ZJW on reversing drug-resistance by CCK-8 assay and flow cytometry analysis in vitro. The protein expression of P-gp, MRP-2, LRP, and ABCB1 mRNA expression level were evaluated by Western blot and quantitative RT-PCR. The activities of PI3K/Akt/NF-κB pathway were also examined with or without ZJW, including Akt, IκB, p65 and their phosphorylation expression.ResultsWe found that ZJW significantly enhanced the sensitivity of chemotherapeutic drugs and increased oxaliplatin (L-OHP)-induced cell apoptosis in a time- and dose-dependent manner. Moreover, both ZJW and a PI3K specific inhibitor (LY294002) suppressed phosphorylation of Akt (Ser473) and NF-κB, which is necessary in the activation of the PI3K/Akt/NF-κB pathway. The effect of ZJW in reversing drug-resistance and suppressing phosphorylation of Akt (Ser473) and NF-κB were weakened after treatment with a PI3K/Akt activator in HCT116/L-OHP cells.ConclusionsOur study has provided the first direct evidence that ZJW reverses drug-resistance in human colorectal cancer by blocking the PI3K/Akt/NF-κB signaling pathway, and could be considered as a useful drug for cancer therapy.

【 授权许可】

Unknown   
© Sui et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.