Establishment and partial characterization of an epirubicin-resistant gastric cancer cell line with upregulated ABCB1

Aledson Vitor Felipe1, Andrea Aparecida Moraes, Juliana de Oliveira

  • 1Department of Medicine, Gastroenterology Division, Federal University, Sao Paulo, Brazil

Insights

Researchers developed epirubicin-resistant gastric cancer cells (AGS/EPI). This multidrug resistance (MDR) is linked to increased expression of the ABCB1 gene, which encodes P-glycoprotein (Pgp).

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Multidrug resistance (MDR) significantly hinders effective chemotherapy for gastric cancer.
  • Understanding the mechanisms of acquired drug resistance is crucial for improving treatment outcomes.

Purpose of the Study:

  • To establish an epirubicin-resistant gastric cancer cell subline (AGS/EPI).
  • To investigate the molecular mechanisms underlying acquired epirubicin resistance in gastric cancer cells.

Main Methods:

  • Parental AGS gastric cancer cells were exposed to stepwise increasing concentrations of epirubicin (EPI) to develop a resistant subline.
  • Quantitative analysis was performed to determine the level of epirubicin resistance.
  • Messenger RNA (mRNA) expression levels of the ATP-dependent drug-efflux pump P-glycoprotein (Pgp), also known as ABCB1 protein, were analyzed.

Main Results:

  • The established AGS/EPI cell subline exhibited a 2.52-fold increase in epirubicin resistance compared to the parental AGS cells.
  • A significant upregulation of mRNA expression for the ABCB1 gene was observed in the AGS/EPI cells.
  • The findings indicate a correlation between ABCB1 gene overexpression and acquired epirubicin resistance.

Conclusions:

  • An epirubicin-resistant gastric cancer cell subline (AGS/EPI) was successfully established.
  • The primary mechanism contributing to acquired epirubicin resistance in this model involves the overexpression of the ABCB1 gene.
  • These findings provide insights into MDR in gastric cancer and potential therapeutic targets.

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...
2.6K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.0K
ABC Transporters: Exporter01:31

ABC Transporters: Exporter

ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
5.7K