1. Spica Prunellae Extract Enhances Fluorouracil Sensitivity of 5-Fluorouracil-Resistant Human Colon Carcinoma HCT-8/5-FU Cells via TOP2α and miR-494.
- Author
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Fang, Yi, Yang, Chi, Zhang, Ling, Wei, Lihui, Lin, Jiumao, Zhao, Jinyan, and Peng, Jun
- Subjects
FLUOROURACIL ,APOPTOSIS ,CARRIER proteins ,CELL death ,CELL lines ,CELL physiology ,COMBINATION drug therapy ,COLON tumors ,DRUG resistance in cancer cells ,DRUG synergism ,ETHANOL ,GENE expression ,HERBAL medicine ,CHINESE medicine ,METABOLISM ,RNA ,BIOINFORMATICS ,GENE expression profiling ,MICRORNA ,RNA-binding proteins - Abstract
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 TOP2α 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 TOP2α 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 TOP2α being significantly suppressed, which increased by 5-FU. Consistently, miR-494, which reportedly regulates TOP2α, 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. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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