Effect Of 5-Fluorouracil On The Expression Of Human Decorin Proteins "Invitro study"
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Objectives The objectives of this study were to focus on investigating the effect of the standard anti-cancer drug 5 Fluorouracil (5-FU) on the expression of human Decorin (HDCN) proteins, the calculation of half maximal inhibitory concentration (IC50), and selectivity index (SI) using the neoplastic model SW620 colorectal adenocarcinoma cell line as compared with the normal human embryonic kidney (HEK293) cell line using the flow cytometry technique. Materials and Methods The expression of HDCN was investigated in both SW620 and HEK293 cell lines after 24, 48 and 72 hours of 5-FU treatment by achievement of a flow cytometry assay using specific HDCN antibodies. IC50 and SI concerning HDCN expression were calculated for 5-FU. Results The preliminary RCSB PDB findings revealed that h uman DCN generally contains four groups of ligands, including acetate, 1, 2-Ethanediol or ethylene glycol, phosphate, and sulfate ions. Virtual docking revealed classic hydrogen bonds between Ser111 (chain B) and Pro67 (chain A). A halogen bond was observed in reference to Leu109 (chain B). π-Alkyl, van der Waals, and carbon-hydrogen interactions were also observed. The IC50 showed considerable results against SW620 cells, with a positive safety margin against HEK293 cells. The values of IC50 for 5-FU after 24, 48 and 72 were respectively recorded as 0.449µg/ml, 3.07µg/ml and 0.498µg/ml on SW620 cell line, and 0.46µg/ml, 33.113µg/ml and 12.882µg/ml on HEK293 cells. The therapeutic selectivity index was exponentially elevated and positively correlated with the incubation intervals, being equal to 1.024, 10.786 and 25.867 respectively, after 24, 48 and 72 hours of 5-FU treatment. Conclusion Human DCN was up regulated in SW620 cell line after treatment with 5-fluorouracil but the latter still has a positive therapeutic index concerning the safety margin toward HEK293 cell line.