Spica Prunellae Extract Enhances Fluorouracil Sensitivity of 5-Fluorouracil-Resistant Human Colon Carcinoma HCT-8/5-FU Cells via TOP2 alpha and miR-494
文献类型： 外文期刊
作者： Fang, Yi 1 ; Yang, Chi 3 ; Zhang, Ling 1 ; Wei, Lihui 1 ; Lin, Jiumao 1 ; Zhao, Jinyan 1 ; Peng, Jun 1 ;
作者机构： 1.Fujian Univ Tradit Chinese Med, Acad Integrat Med, Fuzhou 350122, Fujian, Peoples R China
2.Fujian Univ Tradit Chinese Med, Fujian Key Lab Integrat Med Geriatr, Fuzhou 350122, Fujian, Peoples R China
3.Fujian Acad Agr Sci, Inst Edible Fungi, Fuzhou 350003, Fujian, Peoples R China
期刊名称：BIOMED RESEARCH INTERNATIONAL （ 影响因子：3.411； 五年影响因子：3.62 ）
ISSN： 2314-6133
年卷期： 2019 年 2019 卷
页码：
收录情况： SCI
摘要： The use of 5-fluorouracil (5-FU) has been proven benefits, but it also has adverse events in colorectal cancer (CRC) chemotherapy. In this study, we explored the mechanism of 5-FU resistance by bioinformatics analysis of the NCBI public dataset series GSE81005. Fifteen hub genes were screened out of 582 different expressed genes. Modules of the hub genes in protein-protein interaction networks gathered to TOP2 alpha showed a decrease in HCT-8 cells but an increase in 5-FU-resistant HCT-8/5-FU cells with 5-FU exposure. Downregulation of TOP2 alpha with siRNA or miR-494 transfection resulted in an increase of cytotoxicity and decrease of cell colonies to 5-FU for HCT-8/5-FU cells. Moreover, we found that an ethanol extract of Spica Prunellae (EESP), which is a traditional Chinese medicine with clinically beneficial effects in various cancers, was able to enhance the sensitivity of 5-FU in HCT-8/5-FU cells and partly reverse the 5-FU resistance effect. It significantly helped suppress cell growth and induced cell apoptosis in HCT-8/5-FU cells with the expression of TOP2 alpha being significantly suppressed, which increased by 5-FU. Consistently, miR-494, which reportedly regulates TOP2 alpha, exhibited reverse trends in EESP/5-FU combination treatment. These results suggested that Spica Prunellae may be beneficial in the treatment of 5-FU-resistant CRC patients.
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