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Open Access Research article

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

Hua Sui1, Shu-Fang Pan2, Yu Feng3, Bao-Hui Jin1, Xuan Liu1, Li-Hong Zhou1, Feng-Gang Hou4, Wen-Hai Wang1, Xiao-Ling Fu1, Zhi-Fen Han1, Jian-Lin Ren4, Xiao-Lan Shi2, Hui-Rong Zhu1 and Qi Li1*

Author Affiliations

1 Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

2 Interventional Cancer Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

3 Department of General Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

4 Department of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai 200071, China

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BMC Complementary and Alternative Medicine 2014, 14:279  doi:10.1186/1472-6882-14-279

Published: 1 August 2014

Abstract

Background

Zuo-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.

Methods

We 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.

Results

We 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.

Conclusions

Our 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.

Keywords:
Drug-resistance; Akt; NF-κB; ABCB1; ZJW