Inhibition of PGE₂/EP4 receptor signaling enhances oxaliplatin efficacy in resistant colon cancer cells through modulation of oxidative stress.

ABSTRACT: The platinum-based chemotherapeutic agent, oxaliplatin, is used to treat advanced colorectal cancer (CRC). Unfortunately, nearly all patients acquire resistance to oxaliplatin after long-term use, limiting its therapeutic efficacy. Since COX-2 and PGE₂ signaling can impact colon cancer cell proliferation and survival, we examined how this pathway was affected in an oxaliplatin resistant colon cancer cell line. PGE₂ levels were significantly elevated in oxaliplatin-resistant HT29 cells (OXR) compared to naïve parental HT29 cells (PAR). This increase was associated with elevated COX-2 (17.9-fold; P = 0.008) and reduced 15-hydroxyprostaglandin dehydrogenase (2.9-fold; P < 0.0001) expression. RNAi knockdown of microsomal prostaglandin E synthase-1, the rate-limiting enzym

SUBMITTER: Huang H 

PROVIDER: S-EPMC6427013 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature