Assessment of the Influence of 5-fluorouracil on the SMAD4 Gene Expression, Apoptosis induction and DNA Damage in the Human CACO-2 Cell Line release_mgloyg36grandbdtq4fvlpzhqi

Abstract

<jats:title>Abstract</jats:title> Colorectal cancer (CRC) is the third most common cancer in the world. There are two major distinct precursor lesion pathways: the traditional adenoma–carcinoma pathway leading to most cases CRC, and the serrated neoplasia pathway. <jats:italic>SMAD4</jats:italic> gene is involved in adenoma–carcinoma pathway. The protein encoded by the <jats:italic>SMAD4</jats:italic> gene is a key downstream signaling mediator in the TGFβ pathway. This pathway has tumor-suppressor functions, including cell-cycle arrest and apoptosis. Its activation in late-stage cancer can promote tumorigenesis, including metastasis and chemoresistance. This study aimed to evaluate the effect of 5-fluorouracil (5-FU) on viability of advanced colorectal cancer cells and establishing whether the test compound may have an effect on the expression level of the <jats:italic>SMAD4</jats:italic> gene, DNA damage and apoptosis. Chemotherapy based on 5-FU is used as an adjuvant treatment in most colorectal cancer patients. The results obtained in the study showed that the use of 5-FU in low concentrations may not have a therapeutic effect, and may also influence drug resistance in cancer cells. Moreover, it has been shown that by using 5-FU at higher concentrations and prolonging the exposure time, <jats:italic>SMAD4</jats:italic> gene expression is significantly increased which may have an impact on the effectiveness of the therapy.
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