SUBMISSIONS

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Bayram Ouz ZER, lker DIBIRDIK
 


Keywords:



DESIGN, EXPERIMENTATION AND COMPUTERIZED AUTOMATED DATA ANALYSIS OF DRUG COMBINATIONS AGAINST HT-29 HUMAN COLORECTAL CANCER CELLS BY GALLIC ACID AND CETUXIMAB
 
The aim of this study was to investigate whether gallic acid has a synergistic antiproliferative effect with cetuximab on the proliferation of HT-29 human colorectal cancer cells in vitro. HT-29 cells were plated at a density of 2.5x104 cells per ml into 96-well flat-bottomed microplates and incubated for 24h to allow sufficient cell adhesion, then treated with various concentrations of gallic acid, cetuximab, or their combination. After 24h drug exposure, drug containing media was removed and fresh media was added. HT-29 cells were incubated additional 48h. After incubation, 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazoliumbromide (MTT) cell proliferation assay was performed. On the basis of the proliferation inhibition curve for each single drug, we analyzed the effects of the drug combinations using mass-action law based median effect equation described by Chou and Talalay and the CompuSyn software for automated analysis. Compared to the single administration of gallic acid, the combined administration of gallic acid with cetuximab showed no higher anti-proliferative activity. Combination index values at dose levels IC50/16, IC50/8, and IC50/4 were calculated as 2.1799, 1.5348 and 2.8912, respectively. In conclusion, the results clearly demonstrate that two-drug combination of gallic acid with cetuximab showed antagonistic cytotoxicity in HT-29 cells in vitro. Our findings suggest that the simultaneous administration of gallic acid and cetuximab is not appropriate for in vitro colorectal cancer therapy. Nonetheless, more in-depth studies are required to confirm these results. And, further studies will be required to clarify the molecular and biochemical mechanisms responsible for these antagonistic interactions. ORCID NO: 0000-0003-2833-3133

Anahtar Kelimeler: Cetuximab, Colorectal cancer, Combination therapy, Combination index, Gallic acid