Targeting the mevalonate pathway enhances the efficacy of 5-fluorouracil by regulating pyroptosis.

ABSTRACT: The 5-fluorouracil (5-FU)-based chemotherapy regimen is a primary strategy for treating pancreatic cancer (PC). However, challenges related to 5-FU resistance persist. Investigating the mechanisms of 5-FU resistance and identifying a clinically viable therapeutic strategy are crucial for improving the prognosis of PC. Here, through clinical samples analysis, we found that the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme in mevalonate metabolism, is negatively correlated with the efficacy of 5-FU treatment. There is a significant correlation between HMGCR and the pyroptosis marker gasdermin D (GSDMD), and the HMGCR inhibitor simvastatin can significantly inhibit the activation of pyroptosis signaling. The exogenous addition of geranylgerany

SUBMITTER: Xing Z 

PROVIDER: S-EPMC11579105 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature