AI Article Synopsis
- Anti-cancer drug resistance poses a significant challenge for colorectal cancer (CRC) patients, particularly with 5-fluorouracil (5FU) treatment.
- Recent studies indicate that CRC cells can become resistant to 5FU, and in such cells, PGC-1α expression is notably higher compared to sensitive cells, leading to enhanced mitochondrial functions and reduced cell death.
- This research suggests that targeting PGC-1α could offer new strategies to combat drug resistance in CRC patients.
Article Abstract
Anti-cancer drug resistance is a serious issue for patients with colorectal cancer (CRC). Although recent studies have shown the mechanism by which CRC cells become drug resistant, novel strategies for overcoming this drug resistance have not yet been developed. To address this problem, we characterized 5-fluorouracil (5FU)-resistant CRC cells after treatment with 5FU, and focused on the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in these cells. In 5FU-resistant CRC cells, the 5FU did not considerably decrease the mitochondrial biogenesis or mitochondrial complex I and IV activities, and only partially decreased the antioxidant enzymatic activity, oxygen consumption ratio, and cell survival. The expression of PGC-1α was remarkably increased in the 5FU-resistant CRC cells compared with the 5FU-sensitive CRC cells. The 5FU-resistant CRC cells displayed enhanced mitochondrial biogenesis, oxidative phosphorylation, and antioxidant enzyme activities against 5FU-induced reactive oxygen species, because of the increased expression of PGC-1α. PGC-1α inhibited 5FU-induced endoplasmic reticulum (ER) stress in the 5FU-resistant CRC cells, resulting in the suppression of apoptosis. These findings reveal that PGC-1α plays an important role in drug resistance in 5FU-resistant CRC cells. Moreover, PGC-1α could serve as a novel target in patients with 5FU-resistant CRC.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480203 | PMC |
| http://dx.doi.org/10.3390/ijms20071707 | DOI Listing |
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