Related Experiment Video
Updated: Dec 19, 2025

Author Spotlight: Genetic Profiling for Fluorouracil Response in Gastric Cancer
Published on: May 10, 2024
Cell Cycle Dysregulation Is Associated With 5-Fluorouracil Resistance in Gastric Cancer Cells
DA Som Kim1, Kyoungmi Min1, Suk Kyeong Lee2
1Department of Medical Life Sciences, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Background/Aim:
5-Fluorouracil (5-FU) is an anticancer drug commonly used to treat gastric cancer; however, continuous 5-FU chemotherapy causes drug resistance.
Materials And Methods:
We established five sublines of 5-FU-resistant AGS gastric cancer cells to investigate changes that may have occurred in the development of 5-FU resistance. Drug resistance to other chemotherapeutic reagents, proliferation, cell-cycle changes, and wound healing ability were assessed for each subline.
Results:
Retarded cell growth, G0/G1 phase arrest, up-regulation of p57, and down-regulation of cyclin D1 were commonly observed in all five sublines. Resistance to paclitaxel and cisplatin was also observed in most of the sublines.
Conclusion:
Our data support the notion that G0/G1 arrest due to changes in p57 and cyclin D1 expression may confer drug resistance, while EMT seems non-essential to 5-FU resistance in AGS gastric carcinoma cells.
Insights
Continuous chemotherapy with 5-Fluorouracil (5-FU) can lead to drug resistance in gastric cancer. This study found that cell cycle arrest and altered protein expression, not EMT, are key factors in developing 5-FU resistance.
Area of Science:
- Oncology
- Cancer Biology
- Pharmacology
Background:
- 5-Fluorouracil (5-FU) is a primary chemotherapeutic agent for gastric cancer.
- Acquired resistance to 5-FU limits treatment efficacy.
- Understanding resistance mechanisms is crucial for improving gastric cancer therapy.
Purpose of the Study:
- To investigate molecular and cellular changes associated with 5-FU resistance in gastric cancer cells.
- To determine the role of cell cycle regulation and epithelial-mesenchymal transition (EMT) in 5-FU resistance.
Main Methods:
- Established five sublines of 5-FU-resistant AGS gastric cancer cells.
- Assessed cross-resistance to other chemotherapeutic agents (paclitaxel, cisplatin).
- Evaluated changes in cell proliferation, cell-cycle distribution, and wound healing capacity.
Main Results:
- Commonly observed: retarded cell growth and G0/G1 phase arrest across all resistant sublines.
- Consistent molecular changes: upregulation of p57 and downregulation of cyclin D1.
- Acquired cross-resistance to paclitaxel and cisplatin in most sublines.
Conclusions:
- G0/G1 cell cycle arrest, driven by altered p57 and cyclin D1 expression, is implicated in 5-FU resistance.
- Epithelial-mesenchymal transition (EMT) does not appear essential for 5-FU resistance in this model.
- These findings provide insights into mechanisms of chemotherapy resistance in gastric cancer.
Related Concept Videos
Treatment Resistant Cancers
DNA Damage can Stall the Cell Cycle
DNA Damage Can Stall the Cell Cycle
Mitogens and the Cell Cycle
Molecular Factors Affecting Cell Division
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...

