Journal
CANCER CHEMOTHERAPY AND PHARMACOLOGY
Volume 80, Issue 2, Pages 395-403Publisher
SPRINGER
DOI: 10.1007/s00280-017-3365-y
Keywords
Visfatin; CRC; Dox; MDR1; p65
Categories
Funding
- National Natural Science Fund from the National Natural Science Foundation of China [81672427]
Ask authors/readers for more resources
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-beta, 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 immuno-precipitation (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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available