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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?

SUBMITTER: Huang H

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

REPOSITORIES: biostudies-literature

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

Huang Huakang H Aladelokun Oladimeji O Ideta Takayasu T Giardina Charles C Ellis Lee M LM Rosenberg Daniel W DW

Scientific reports 20190320 1

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 ...[more]

PMID: 30894570

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