Purpose: Suppressor of mothers against decapentaplegic homolog 4 (SMAD family member 4, ) is involved in the adenoma-carcinoma pathway, leading to the development of colon cancer. The encoded protein 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. Most colorectal cancer patients receive chemotherapy based on 5-FU as an adjuvant treatment. However, the success of therapy is hampered by multidrug resistance by neoplastic cells. In colorectal cancer, resistance to 5-FU-based therapy is influenced by gene expression, as patients with decreased gene expression probably have a higher risk of developing 5-FU-induced resistance. The mechanism leading to the development of this phenomenon is not fully understood. Therefore, the present study assesses the possible influence of 5-FU on changes in the expression of the and genes.
Patients And Methods: The effect of 5-FU on the expression of and in colorectal cancer cells derived from the CACO-2, SW480 and SW620 cell lines was evaluated using real-time PCR. The cytotoxicity of 5-FU on colon cancer cells was assessed by the MTT method, and its effect on the induction of cell apoptosis and the initiation of DNA damage using a flow cytometer.
Results: Significant changes in the level of and gene expression were noted in the CACO-2, SW480 and SW620 cells treated with 5-FU at various concentrations during 24 h and 48 h exposure. The use of 5-FU at a concentration of 5 µmol/L resulted in a decrease in the expression of the gene in all cell lines at both exposure times, while the concentration of 100 µmol/L increased the expression of the gene in CACO-2 cells. The level of expression of the gene was higher for all cells treated with 5-FU at the highest concentrations, while the exposure time was extended to 48 h.
Conclusion: The observed in vitro changes in CACO-2 cells caused by 5-FU may be of clinical relevance when choosing the drug concentration for treating patients with colorectal cancer. It is possible that 5-FU has a stronger effect on colorectal cancer cells at the higher concentrations. Low concentrations of 5-FU may not have a therapeutic effect and may also influence drug resistance in cancer cells. Higher concentrations and prolonged exposure time may affect gene expression, which may increase the effectiveness of therapy.
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http://dx.doi.org/10.3390/bioengineering10050570 | DOI Listing |
Oncol Rep
February 2025
Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
BH3 mimetics are small‑molecule inhibitors of the antiapoptotic Bcl‑2 family and have therapeutic efficacy against hematological malignancies. BH3 mimetic A‑1331852 suppresses colorectal cancer cell proliferation. Progressive resistance to the widely used anticancer agent fluorouracil (5‑FU) is a key reason for colorectal cancer recurrence; therefore, the present study tested if A‑1331852 can suppress the proliferation of 5‑FU‑resistant colorectal cancer cells.
View Article and Find Full Text PDFJ Med Virol
December 2024
Division of Microbiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, Japan.
Placental trophoblasts constitute the interface between the fetal and maternal environments and physically prevent maternal-fetal viral transmission. However, congenital human cytomegalovirus (HCMV) infection in the early stages of pregnancy results in severe symptoms in the fetus. HCMV is the most common causative agent of intrauterine infection.
View Article and Find Full Text PDFMol Ecol
December 2024
Department of Integrative Biology, University of Texas at Austin, Austin, Texas, USA.
Coral populations across the Great Barrier Reef (GBR) could rapidly adapt to the warming climate if they have standing genetic variation for thermal tolerance. Here, we describe a locus likely involved in latitudinal adaptation of Acropora millepora. This locus shows a steep latitudinal gradient of derived allele frequency increasing at higher latitudes, and harbours a cluster of eight tandemly repeated Δ9-desaturase genes adjacent to a region in the genome where a hard selective sweep likely occurred.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Department of Anorectal, Affiliated Hospital of Jiaxing University, The Second Hospital of Jiaxing, Jiaxing City, Zhejiang Province, China.
The underlying regulating mechanisms of miR-105-5p/PTEN in colon cancer (CC) progression are still unknown. MiR-105-5p and PTEN expressions were determined using RT-PCR. PTEN protein levels were examined by western blot.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Increasing long noncoding RNAs (lncRNAs) have been found to participate in regulating the progression of colorectal cancer (CRC), which is a common gastrointestinal malignancy. Here, the specific role and mechanisms of lncRNA LINC00294 were investigated in CRC. The expression levels of LINC00294, miR-499a-5p, and La-related protein 4B (LARP4B) in CRC cells (HCT116 and SW620) and tissues were assessed by RT-qPCR.
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