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Tamoxifen Downregulates the Expression of Notch1 and DLL1 Genes in MKN-45 Gastric Cancer Cells

Faranak Khanipouyani1, Hassan Akrami2

  • 1Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran.

Journal of Gastrointestinal Cancer
|September 9, 2020
PubMed
Abstract

Insights

Tamoxifen, a repurposed drug, was found to downregulate Notch1 and DLL1 gene expression in gastric cancer cells. This suggests a potential mechanism for tamoxifen's anti-cancer effects in this disease.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Gastric cancer is a leading cause of cancer mortality globally.
  • Tamoxifen is known for its anti-tumor effects in breast cancer.
  • The impact of tamoxifen on Notch signaling in gastric cancer remains unexplored.

Purpose of the Study:

  • To investigate the effects of tamoxifen on Notch1 and DLL1 gene expression in the MKN-45 gastric cancer cell line.
  • To explore tamoxifen as a potential repurposed drug for gastric cancer treatment.

Main Methods:

  • MKN-45 cells were treated with varying concentrations of tamoxifen.
  • Cell viability was assessed using the trypan blue exclusion assay.
  • Quantitative real-time PCR was employed to measure Notch1 and DLL1 mRNA levels post-treatment.

Main Results:

  • Tamoxifen exhibited dose-dependent cytotoxicity against MKN-45 cells, with a CC50 of approximately 200 μM.
  • A 100 μM dose of tamoxifen significantly downregulated Notch1 mRNA by 24% and DLL1 mRNA by 92% compared to controls.

Conclusions:

  • Tamoxifen interferes with the Notch signaling pathway in gastric cancer cells.
  • Downregulation of Notch1 and DLL1 gene expression by tamoxifen may contribute to its anti-cancer activity in gastric cancer.
Keywords:
DLL1Gastric cancerMKN-45Notch1Repurposed drugTamoxifen

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