Spica Prunellae Extract Enhances Fluorouracil Sensitivity of 5-Fluorouracil-Resistant Human Colon Carcinoma HCT-8/5-FU Cells via TOP2α and miR-494

• Published in: BioMed research international 2019, Vol.2019 (2019), p.1-12
• Main Authors: Peng, Jun, Lin, Jiumao, Wei, Lihui, Zhang, Ling, Yang, Chi, Fang, Yi, Zhao, Jinyan
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Angiogenesis; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Bioinformatics; Biomedical research; Cancer; Cancer therapies; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Proliferation - genetics; Chemotherapy; Colon; Colon - drug effects; Colonic Neoplasms - drug therapy; Colonic Neoplasms - genetics; Colorectal cancer; Colorectal carcinoma; Cytotoxicity; DNA Topoisomerases, Type II - genetics; Down-Regulation - drug effects; Down-Regulation - genetics; Drug resistance; Drug Resistance, Neoplasm - drug effects; Drug Resistance, Neoplasm - genetics; Ethanol; Fluorouracil - pharmacology; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - genetics; Genes; Genomics; Herbal medicine; Humans; Liver cancer; Medical research; Medicine, Chinese Traditional - methods; MicroRNAs; Mortality; Plant Extracts - pharmacology; Poly-ADP-Ribose Binding Proteins - genetics; Protein expression; Protein interaction; Proteins; Sensitivity enhancement; Signal Transduction - drug effects; Signal Transduction - genetics; siRNA; Software; Toxicity; Traditional Chinese medicine; Transfection
• ISSN: 2314-6133; 2314-6141; 2314-6141
• DOI: 10.1155/2019/5953619

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.