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EXPLORING THE POTENTIAL OF METFORMIN AND CELECOXIB AS NEW ADJUVANT THERAPY FOR COLORECTAL CANCER

Haniye Rahimi Kolour 1

Affiliations

1 Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Islamic Republic of

Summary

AI Generated

A gene expression analysis study investigated metformin and celecoxib combination therapy as potential adjuvant treatment for colorectal cancer, identifying ID1 as a commonly expressed gene in response to both drugs.

Gene expression analysis of metformin and celecoxib datasets (GSE11237 and GSE67342) identified ID1 as the only commonly expressed gene in both, with network analysis revealing associated genes MYOD1, SMAD4, SMAD9, SMAD5, and TCF3 in the TGFB pathway.
The study protocol includes MTT assay, apoptosis, and cell cycle analysis on CaCO2 and SW48 cell lines, with real-time PCR planned to assess expression of ID1 and SMAD4 genes.
Both metformin and celecoxib are established drugs with known anti-cancer properties, making them candidates for cost-effective drug repurposing in colorectal cancer treatment.
The authors suggest their findings indicate potential for metformin-celecoxib combination as adjuvant therapy and provide basis for understanding molecular mechanisms, though in vitro validation assays are still to be performed.

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This summary was generated by an AI large language model based on the content transcript. It is for informational purposes only and should not be considered a substitute for clinical judgment. Always rely on your professional expertise and the full clinical context when making clinical decisions.

Abstract

Introduction

Colorectal cancer (CRC) is a global health concern, with high mortality rates and limited success in early detection and effective treatment of metastatic disease. While conventional treatments such as surgery, chemotherapy, and radiation therapy have shown some success, there is still a need for new and more effective treatment options. Repurposing existing drugs for cancer treatment has gained increasing attention due to its cost-effective nature and the availability of a large number of approved drugs with established safety profiles. In this study, we investigate the potential of using metformin and celecoxib as adjuvant agents for CRC treatment. Both drugs have been shown to have anti-cancer properties and are well-established for the treatment of other conditions. By analyzing gene expression data sets for these drugs and performing in vitro assays, we aim to evaluate their effectiveness as combination therapy and explore the underlying mechanisms of action.

Aims & Methods

Gene expression data sets for these drugs were obtained from the GEO database (GSE11237 and GSE67342) and analyzed using the R Limma package. Fold-change (FC; value > 1) and p-value ≤ 0.05 are considered as DEG selection criteria. MTT assay, apoptosis, and cell cycle analysis will be performed to evaluate the cytotoxic effect of these drugs on CaCO2 and SW48 cell lines. Furthermore, to assess the expression of the candidate genes identified in the in-silico phase, we will perform real-time PCR analysis.

Results

After performing gene expression analysis using the R Limma package, we found that only one gene, ID1, was identified as commonly expressed in both datasets. STRING server was used to find the intermediate network between ID1 and other human genes. Finally, the resulting gene network was determined by using Gephi software. Based on this, three modules were obtained. The genes in the module containing ID1 are MYOD1, SMAD4, SMAD9, SMAD5, and TCF3. Among the resulting genes, considering that ID1 is a hub gene and the functional pathway of this gene is TGFB. We selected the SMAD4 gene, which plays a role in this pathway, as a companion gene to determine the expression level of these two genes in treatment with both drugs.
Our results suggest a potential functional role for ID1 in the cellular response to treatment with the drugs metformin and celecoxib in CRC.

Conclusion

In conclusion, our study provides evidence that the combination therapy of metformin and celecoxib may have the potential as adjuvant therapy for CRC. These findings contribute to the understanding of the molecular mechanisms underlying the therapeutic effects of these drugs in CRC and provide a basis for the development of new adjuvant therapies that could improve patient outcomes and reduce healthcare costs.

Conference

UEG Week Copenhagen 2023

Topics

Colorectal

Submission format

Abstract

Session

PP 06 Other lower GI disorders (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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A DUAL ROLE FOR IFNG IN EPITHELIAL INJURY AND CRYPT HYPERPLASIA IN CELIAC DISEASE

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