Acriflavine enhances the antitumor activity of the chemotherapeutic drug 5‑fluorouracil in colorectal cancer cells

Zargar,Parisa; Ghani,Esmaeel; Mashayekhi,Farideh Jalali; Ramezani,Amin; Eftekhar,Ebrahim

doi:10.3892/ol.2018.8569

Acriflavine enhances the antitumor activity of the chemotherapeutic drug 5‑fluorouracil in colorectal cancer cells

Authors:
- Parisa Zargar
- Esmaeel Ghani
- Farideh Jalali Mashayekhi
- Amin Ramezani
- Ebrahim Eftekhar
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Affiliations: Student Research Committee, Hormozgan University of Medical Sciences, Bandar Abbas 7919915519, Iran, Department of Physiology, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas 7919915519, Iran, Department of Biochemistry and Genetics, Arak University of Medical Sciences, Arak 3813653555, Iran, Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz 7134845794, Iran, Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas 7919915519, Iran
Published online on: April 25, 2018 https://doi.org/10.3892/ol.2018.8569
Pages: 10084-10090

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Abstract

5‑Fluorouracil (5‑FU)‑based chemotherapy improves the overall survival rates of patients with colorectal cancer (CRC). However, only a small proportion of patients respond to 5‑FU when used as a single agent. The aim of the present study was to investigate whether the anticancer property of 5‑FU is potentiated by combination treatment with acriflavine (ACF) in CRC cells. Additionally, the potential underlying molecular mechanisms of the cytotoxic effect of ACF were determined. The cytotoxic effects of ACF, 5‑FU and irinotecan on different CRC cell lines with different p53 status were investigated using an MTT assay. SW480 cells that express a mutated form of p53 and two other CRC cell lines were used, HCT116 and LS174T, with wild‑type p53. To determine the effect of ACF on the sensitivity of cells to 5‑FU, cells were co‑treated with the 30% maximal inhibitory concentration (IC30) of ACF and various concentrations of 5‑FU, or pretreated with the IC30 of ACF and various concentrations of 5‑FU. To assess the mechanism of action of ACF, cells were treated with IC30 values of the compound and then the reverse transcription‑quantitative polymerase chain reaction was used to evaluate mRNA levels of hypoxia‑inducible factor‑1α (HIF‑1α) and topoisomerase 2. Results indicate that pretreatment with ACF markedly sensitized CRC cells to the cytotoxic effects of 5‑FU, whereas simultaneous treatment with ACF and 5‑FU were not able to alter the resistance of CRC cells to 5‑FU. In comparison with irinotecan, ACF was a more potent agent for enhancing the antitumor activity of 5‑FU. ACF did not alter the mRNA levels of either HIF‑1α or topoisomerase 2. The results of the present study reveal for the first time that pretreatment of CRC cells with ACF markedly increases the cytotoxic effects of 5‑FU, regardless of the p53 status of cells.

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