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Visfatin mediates doxorubicin resistance in human colorectal cancer cells via up regulation of multidrug resistance 1 (MDR1)

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Abstract

Colorectal cancer (CRC) is one of the prevalent and deadly cancers worldwide. Chemotherapy resistance is one of the most challenging problems for CRC and other cancer treatments. Recent studies indicated that increasing levels of visfatin are correlated with worse clinical prognosis of CRC patients, while the effects and mechanisms of visfatin on progression of CRC remain unclear. Our present study established doxorubicin (Dox)-resistant CRC HCT-116 and SW480 cells (named HCT-116 Dox/R and SW480 Dox/R). The expression of visfatin, while not IL-6, IL-8, or TGF-β, in CRC Dox-resistant cells was significantly greater than that in their parental cells, while knockdown of visfatin by its specific siRNAs can elevate Dox sensitivity of CRC-resistant cells. In addition, si-visfatin can significantly down regulate the expression of multidrug resistance 1 (MDR1), while not multidrug resistance-associated protein 1 or lung resistance-related protein, in both HCT-116 Dox/R and SW480 Dox/R cells. Visfatin can regulate the transcription of MDR1 via modulating its promoter activities. Si-visfatin can also decrease the activation and nuclear localization of p65, one of the most important transcription factors for the expression of MDR1. Chromatin immunoprecipitation (ChIP) indicated that si-visfatin can suppress the binding between p65 and MDR1 promoter. Collectively, our present study revealed that visfatin mediates the Dox resistance of CRC cells via up regulation of MDR1. It indicated that targeted inhibition of visfatin might be helpful for overcoming Dox resistance of CRC therapy.

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Acknowledgements

This research was supported by the National Natural Science Fund from the National Natural Science Foundation of China (Grant no. 81672427).

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Authors and Affiliations

  1. Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, No. 44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning, People’s Republic of China

    Xiaofei Yan, Jian Zhao & Rui Zhang

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  1. Xiaofei Yan
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  2. Jian Zhao
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  3. Rui Zhang
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Correspondence to Rui Zhang.

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The authors declare no conflict of interest. There is no human/animal participant in the present study.

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Yan, X., Zhao, J. & Zhang, R. Visfatin mediates doxorubicin resistance in human colorectal cancer cells via up regulation of multidrug resistance 1 (MDR1). Cancer Chemother Pharmacol 80, 395–403 (2017). https://doi.org/10.1007/s00280-017-3365-y

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