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

BMC Complementary and Alternative Medicine

Qi Li¹  Hui-Rong Zhu¹  Xiao-Lan Shi²  Jian-Lin Ren³  Zhi-Fen Han¹  Xiao-Ling Fu¹  Wen-Hai Wang¹  Feng-Gang Hou³  Li-Hong Zhou¹  Xuan Liu¹  Bao-Hui Jin¹  Yu Feng⁴  Shu-Fang Pan²  Hua Sui¹ 

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

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

Others  :  1087109
DOI  :  10.1186/1472-6882-14-279

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

【 摘 要 】

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.

【 授权许可】

   
2014 Sui et al.; licensee BioMed Central Ltd.

【 图 表 】

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