Repurposing an FDA-approved Drug to Target Bronchial Epithelial Mesenchymal Transition

Rosdi, Nor Shamira (2020) Repurposing an FDA-approved Drug to Target Bronchial Epithelial Mesenchymal Transition. [Project Paper] (Submitted)

Text FPSK2 2020 26.pdf Download (1MB)

Abstract

Epithelial mesenchymal transition (EMT) is a biological process which causes cells to transform from epithelial to mesenchymal cell in asthma disease. Previous studies show the transforming growth beta (TGF-β1) is the most potent inducer in the EMT process and later can cause airway remodeling. Current asthma treatment reported to have no significant effect on the airway remodeling. Objective: Thus, this project aims to identify alternative treatment for airway remodeling in asthma by repurposing the FDA-approved drugs that can target TGF-β receptor type 1 (TβR1) kinase domain. Hypothesis: It is hypothesized that repurposing of FDA-approved drugs can target the TβR1 and inhibit bronchial epithelial mesenchymal transition (EMT) in human bronchial epithelial cells. Method: Selection of drugs that are capable of binding to the TβR1 can be obtained from Drug Repositioning Exploration Resource (Drug ReposER) website server. The TGF-β1 and selected drug 3D structures can be retrieved in the Protein Data Bank (PDB) database to proceed with the molecular docking. By using Autodock Vina, a free molecular docking software, the binding affinity of the selected drug can be analyzed. A drug with the best binding affinity will be selected for the in-vitro study on the human bronchial epithelial cells, BEAS 2B cells. Cells will be cultured in BEGM media and will be tested with the selected drugs. MTS assay was used in order to determine the safe concentrations on the BEAS 2B cells. Later, cells will be induced with TGF-β1. The changes in cell morphology will be observed and the quantitative measurement of the radius ratio of cells will be measured. All data from experiment will be subjected to one-way ANOVA and Dunnett’s post hoc test. Result: MTS assay showed no significant toxic effect on the BEAS 2B cells at all concentrations. There is no significant change on the induced BEAS 2B cells morphology upon the treatment of Telmisartan. Conclusion: Telmisartan was found to produce no significant effect on the induced BEAS 2B cells.

Item Type:	Project Paper
Faculty:	Faculty of Medicine and Health Science
Depositing User:	Ms. Nor Safa'aton Saidin
Date Deposited:	23 Aug 2023 00:53
Last Modified:	23 Aug 2023 00:53
URI:	http://psaspb.upm.edu.my/id/eprint/1314

Actions (login required)

View Item