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.

Anticancer Research
|June 4, 2020
PubMed
Abstract

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 Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.6K
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.9K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
2.9K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.6K
Molecular Factors Affecting Cell Division01:27

Molecular Factors Affecting Cell Division

Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit 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...
3.8K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.8K