Gastric cancer cell death analyzed by live cell imaging of spheroids

George Alzeeb1, Danielle Arzur1, Valérie Trichet2

  • 1Univ Brest, Inserm, EFS, UMR 1078, GGB, 29200, Brest, France.

Scientific Reports
|January 28, 2022
PubMed

Insights

Repurposing the cholesterol drug lovastatin with docetaxel effectively eliminates gastric cancer cells in both 2D and 3D models. This combination shows promise as an enhanced adjuvant therapy for advanced gastric cancer.

Area of Science:

  • Oncology
  • Drug Repurposing
  • Cancer Biology

Background:

  • Gastric cancer (GC) is a leading cause of cancer mortality, often diagnosed late.
  • Developing novel therapeutic strategies, including drug repurposing, is crucial for improving patient outcomes.
  • Three-dimensional (3D) spheroid models offer a more physiologically relevant platform for evaluating anti-cancer drug efficacy compared to traditional 2D cultures.

Purpose of the Study:

  • To evaluate the efficacy of combining docetaxel and lovastatin in 3D gastric cancer spheroid models.
  • To assess the potential of lovastatin as an adjuvant therapy for gastric cancer.
  • To compare the effectiveness of this drug combination in 2D versus 3D culture systems.

Main Methods:

  • Established monocellular and bicellular gastric cancer spheroids using HGT-1 and AGS cell lines, with and without cancer-associated fibroblasts.
  • Assessed drug-induced cytotoxicity using MTT assays.
  • Utilized Incucyte live imaging to monitor spheroid growth and apoptosis in response to treatment.

Main Results:

  • The combination of lovastatin and docetaxel demonstrated significant efficacy in eliminating gastric cancer cells in both 2D and 3D spheroid models.
  • The drug combination effectively induced apoptosis in cancer cells within the spheroids.
  • The study confirmed the potent anti-cancer activity of lovastatin when used as an adjuvant to docetaxel.

Conclusions:

  • The lovastatin + docetaxel combination is a potent strategy for gastric cancer treatment, effective in both 2D and 3D culture systems.
  • Lovastatin shows significant potential for repurposing as an adjuvant therapy to taxane-based chemotherapy for gastric cancer.
  • 3D spheroid models are valuable for evaluating the efficacy of novel anti-cancer drug combinations.

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