Apoptotic effect of 5-fluorouracil-doxorubicin combination on colorectal cancer cell monolayers and spheroids.
Humans
Fluorouracil
/ pharmacology
Spheroids, Cellular
/ drug effects
Doxorubicin
/ pharmacology
Apoptosis
/ drug effects
Colorectal Neoplasms
/ drug therapy
HT29 Cells
Cell Proliferation
/ drug effects
Caco-2 Cells
Gene Expression Regulation, Neoplastic
/ drug effects
Proto-Oncogene Proteins c-bcl-2
/ genetics
Cell Line, Tumor
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
Tumor Suppressor Protein p53
/ genetics
bcl-2-Associated X Protein
/ metabolism
5-Fluorouracil
Apoptosis
Colorectal cancer
Doxorubicin
Drug combination
Tumor spheroid
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
02 May 2024
02 May 2024
Historique:
received:
25
01
2024
accepted:
16
04
2024
medline:
3
5
2024
pubmed:
3
5
2024
entrez:
2
5
2024
Statut:
epublish
Résumé
Drug combination studies help to improve new treatment approaches for colon cancer. Tumor spheroids (3D) are better models than traditional 2-dimensional cultures (2D) to evaluate cellular responses to chemotherapy drugs. The cultivation of cancer cells in 2D and 3D cultures affects the apoptotic process, which is a major factor influencing the response of cancer cells to chemotherapeutic drugs. In this study, the antiproliferative effects of 5-fluorouracil (5-FU) and doxorubicin (DOX) were investigated separately and in combination using 2D and 3D cell culture models on two different colon cancer cell lines, HT-29 (apoptosis-resistant cells) and Caco-2 2 (apoptosis-susceptible cells). The effect of the drugs on the proliferation of both colon cancer cells was determined by performing an MTT assay in 2D culture. The apoptotic effect of 5-FU and DOX, both as single agents and in combination, was assessed in 2D and 3D cultures through quantitative real-time polymerase chain reaction analysis. The expression of apoptotic genes, such as caspases, p53, Bax, and Bcl-2, was quantified. It was found that the mRNA expression of proapoptotic genes was significantly upregulated, whereas the mRNA expression of the antiapoptotic Bcl-2 gene was significantly downregulated in both colon cancer models treated with 5-FU, DOX, and 5-FU + DOX. The results indicated that the 5-FU + DOX combination therapy induces apoptosis and renders 5-FU and DOX more effective at lower concentrations compared to their alone use. This study reveals promising results in reducing the potential side effects of treatment by enabling the use of lower drug doses.
Sections du résumé
BACKGROUND
BACKGROUND
Drug combination studies help to improve new treatment approaches for colon cancer. Tumor spheroids (3D) are better models than traditional 2-dimensional cultures (2D) to evaluate cellular responses to chemotherapy drugs. The cultivation of cancer cells in 2D and 3D cultures affects the apoptotic process, which is a major factor influencing the response of cancer cells to chemotherapeutic drugs. In this study, the antiproliferative effects of 5-fluorouracil (5-FU) and doxorubicin (DOX) were investigated separately and in combination using 2D and 3D cell culture models on two different colon cancer cell lines, HT-29 (apoptosis-resistant cells) and Caco-2 2 (apoptosis-susceptible cells).
METHODS
METHODS
The effect of the drugs on the proliferation of both colon cancer cells was determined by performing an MTT assay in 2D culture. The apoptotic effect of 5-FU and DOX, both as single agents and in combination, was assessed in 2D and 3D cultures through quantitative real-time polymerase chain reaction analysis. The expression of apoptotic genes, such as caspases, p53, Bax, and Bcl-2, was quantified.
RESULTS
RESULTS
It was found that the mRNA expression of proapoptotic genes was significantly upregulated, whereas the mRNA expression of the antiapoptotic Bcl-2 gene was significantly downregulated in both colon cancer models treated with 5-FU, DOX, and 5-FU + DOX.
CONCLUSION
CONCLUSIONS
The results indicated that the 5-FU + DOX combination therapy induces apoptosis and renders 5-FU and DOX more effective at lower concentrations compared to their alone use. This study reveals promising results in reducing the potential side effects of treatment by enabling the use of lower drug doses.
Identifiants
pubmed: 38698270
doi: 10.1007/s11033-024-09562-x
pii: 10.1007/s11033-024-09562-x
doi:
Substances chimiques
Fluorouracil
U3P01618RT
Doxorubicin
80168379AG
Proto-Oncogene Proteins c-bcl-2
0
Tumor Suppressor Protein p53
0
bcl-2-Associated X Protein
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
603Subventions
Organisme : Tokat Gaziosmanpaşa University, Foundation of Scientific Researches Projects
ID : Project number: 2022/82
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
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