期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 117, 期 6, 页码 1471-1481出版社
WILEY
DOI: 10.1002/jcb.25451
关键词
COLORECTAL CANCER; MULTIDRUGRESISTANCE; NF-B; ABCG2; EVODIAMINE
资金
- National Natural Science Foundation of China [81202812, 81373862, 81303106, 81473478, 81460704, 81573805]
- Program of Shanghai Municipal Education Commission [12YZ058]
- Shanghai Municipal Health Bureau [2011ZJ030, 2010QL050B]
- Program of Science and Technology [201291169]
- Program of Shanghai Clinical TCM Laboratory [14DZ2273200]
Evodiamine (Evo), extracted from the Chinese herbal medicine Evodia rutaecarpa, has cytotoxic effects on different types of human cancer cells. However, its effects on drug resistance and their molecular mechanism and therapeutic target in colorectal cancer are not well understood. In the present study, we observed that Evo inhibited cell growth and induced apoptosis in adose-and time-dependent manner in HCT-116/L-OHP cells. Moreover, Evo treatment reduced Rhodamine 123 accumulation and ATPase activity in HCT-116/L-OHP cells, indicating that Evo decreased the efflux function in HCT-116/L-OHP cells. Interestingly, phosphorylation of NF-B pathway, particularly p50/p65, was also inhibited by Evo treatment. Furthermore the effect of Evo in reversing drug resistance and suppressing phosphorylation of NF-B pathway were attenuated after treatment with the NF-B activator (LPS). Additionally, Evo inhibited the tumor growth in a colorectal MDR cancer xenograft model and down regulated p-NF-B level in vivo. Our study provided the first direct evidence that Evo can attenuate multidrug resistance by blocking p-NF-B signaling pathway in human colorectal cancer. Evo could be a potential candidate for cancer chemotherapy. J. Cell. Biochem. 117: 1471-1481, 2016. (c) 2015 Wiley Periodicals, Inc.
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