Butyrate-mediated acquisition of chemoresistance by human colon cancer cells
Autor: | So Hee Kim, Chae Kyung Jeon, Hyang Ri Kang, Soo-Jeong Lim, Hyeon Gyeom Choi |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Cancer Research Paclitaxel bcl-X Protein Apoptosis Butyrate Hydroxamic Acids 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor medicine ATP Binding Cassette Transporter Subfamily G Member 2 Humans Neoplasm Invasiveness ATP Binding Cassette Transporter Subfamily B Member 1 neoplasms Cell Proliferation P-glycoprotein biology Oncogene Cell growth Cancer General Medicine HCT116 Cells medicine.disease Molecular biology digestive system diseases Neoplasm Proteins Butyrates 030104 developmental biology Oncology Doxorubicin Drug Resistance Neoplasm Cell culture 030220 oncology & carcinogenesis Colonic Neoplasms Cancer cell biology.protein Fluorouracil Multidrug Resistance-Associated Proteins biological phenomena cell phenomena and immunity |
Zdroj: | Oncology Reports. 36:1119-1126 |
ISSN: | 1791-2431 1021-335X |
DOI: | 10.3892/or.2016.4838 |
Popis: | Butyrate is a short-chain fatty acid produced by the intestinal microflora and it not only induces apoptosis but also inhibits the proliferation of cancer cells. Recently, it has been reported that butyrate may cause resistance in colon cancer cells. Therefore, we investigated the effects of increased resistance to butyrate in HCT116 colon cancer cells. We established HCT116 cells resistant to butyrate (HCT116/BR) by treating HCT116 parental cells (HCT116/PT) with increasing concentrations of butyrate to a maximum of 1.6 mM for 3 months. The butyrate concentrations that inhibited cell growth by 50% (IC50) were 0.508 and 5.50 mM in HCT116/PT and HCT116/BR cells. The values after treatment with paclitaxel, 5-fluorouracil (5-FU), doxorubicin and trichostatin A (TSA) were 2.42, 2.36, 4.31 and 11.3-fold higher, respectively, in HCT116/BR cells compared with HCT116/PT cells. The protein expression of drug efflux pumps, such as P-glycoprotein (P-gp), breast cancer-resistant protein (BCRP) and the multidrug resistance associated protein 1 (MRP1), did not differ between HCT116/PT and HCT116/BR cells. The expression level of the anti-apoptotic Bcl-xL protein was increased while those of pro-apoptotic Bax and Bim proteins were reduced in HCT116/BR cells. There were no significant differences in cell motility and invasion. This study suggests that exposure of colon cancer cells to butyrate results in development of resistance to butyrate, which may play a role in the acquisition of chemoresistance in colon cancer. |
Databáze: | OpenAIRE |
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