INTERNATIONAL CONGRESS OF
PharmacoGenetics
Exploring the Anticancer Mechanisms of Ibuprofen in Gastric Cancer: From Molecular Pathways to Clinical Potential
-
Mohammadamir kakaee,1,*
1. Shahid Beheshti University of Medical Sciences
- Introduction: Gastric cancer is a significant public health concern, ranking as the fifth most common cancer and the third most common cause of cancer death globally. The relationship between stomach cancer and preventive measures, including the use of certain medications, is therefore a crucial area of study. One such medication is ibuprofen, a nonsteroidal anti-inflammatory drug (NSAID) renowned for its analgesic, antipyretic, and anti-inflammatory properties. Ibuprofen's mechanism of action involves non-selective inhibition of cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2, which play a pivotal role in the synthesis of prostaglandins that mediate inflammation and pain.
- Methods: A comprehensive literature search was conducted across two databases: PubMed and the Scientific Information Database (SID). The search spanned from 1988 to 2024 and utilized the keywords "ibuprofen" and "gastric cancer." In the SID database, one relevant study was identified. The search in PubMed initially yielded 39 articles. After applying the inclusion criteria and removing duplicates, a total of 7 articles were selected for further review. These articles were subsequently analyzed to evaluate the relationship between ibuprofen and gastric cancer.
- Results: Research indicates that ibuprofen may have a protective effect against various types of cancer, including stomach cancer. The mechanisms through which ibuprofen exerts its anticancer effects include: 1. Inhibition of Cell Proliferation: Ibuprofen has been shown to reduce cell proliferation in gastric cancer stem cells by inhibiting the Wnt/β-catenin signaling pathway and altering the expression of stemness markers such as CD44, OCT3/4, SOX2, Nanog, and KLF4 [Akrami, 2018]. 2. Modulation of MicroRNAs: Ibuprofen affects the expression of microRNAs that target COX-1/2 mRNA in gastric cancer stem-like cells. This modulation impacts several signaling pathways, including PI3K-Akt, P53, and TGF-beta, which are crucial in cancer development and progression [Akrami, 2019]. 3. Enhancement of Detoxification Enzymes: Ibuprofen increases the activity of glutathione S-transferases (GSTs) in the stomach, which are detoxification enzymes that help in reducing cancer risk by enhancing the detoxification of carcinogens [Lieshout, 1997]. 4. Reduction in Cancer Risk: Epidemiological studies have shown that regular intake of NSAIDs, including ibuprofen, is associated with a significant reduction in the risk of stomach cancer. This protective effect is more pronounced with long-term use [Harris, 2005]. Overall, ibuprofen's anticancer effects are attributed to its ability to inhibit COX enzymes, modulate signaling pathways, and enhance detoxification processes, making it a potential chemopreventive agent against stomach cancer.
- Conclusion: In the discussion section, we summarize the theories and talk about their strengths and weaknesses Theory 1: Inhibition of Cell Proliferation via Wnt/β-Catenin Pathway Ibuprofen has been shown to reduce cell proliferation in gastric cancer stem cells by inhibiting the Wnt/β-catenin signaling pathway and altering the expression of stemness markers. While this theory provides a clear molecular mechanism, it is primarily supported by in vitro studies and requires further validation in clinical settings. Theory 2: Modulation of MicroRNAs Ibuprofen has been found to affect the expression of microRNAs that target COX-1/2 mRNA in gastric cancer stem-like cells, impacting several signaling pathways. This theory highlights the role of microRNAs in cancer therapy and provides a broader understanding of ibuprofen's molecular effects, but is primarily based on cellular models and requires further investigation in clinical settings. Theory 3: Enhancement of Detoxification Enzymes Ibuprofen has been shown to increase the activity of glutathione S-transferases (GSTs) in the stomach, enhancing detoxification processes and reducing cancer risk. While this theory demonstrates a protective mechanism through detoxification, it is based on animal model studies and requires human trials to confirm its findings. Theory 4: Epidemiological Evidence of Risk Reduction Regular intake of NSAIDs, including ibuprofen, has been associated with a significant reduction in the risk of stomach cancer. This theory is supported by large-scale epidemiological studies, but is based on observational data and may be influenced by confounding factors. Theory 5: Phospho-Ibuprofen as a Novel Agent Phospho-ibuprofen, a modified derivative, has been shown to exhibit enhanced anticancer efficacy and reduced toxicity compared to conventional ibuprofen. While this theory demonstrates improved safety and efficacy in preclinical models, it is currently in the preclinical stage and requires clinical trials to validate its potential therapeutic benefits. Each of these theories offers valuable insights into the potential anticancer effects of ibuprofen. However, there remains a critical need for more clinical studies to substantiate these findings and fully elucidate ibuprofen’s role in cancer prevention and therapy.
- Keywords: Ibuprofen Gastric Cancer
