Abstract
Gastric cancer (GC) is the third cause of cancer-related mortality worldwide and is often diagnosed at advanced stages of the disease. This makes the development of more comprehensive models and efficient treatments crucial. One option is based on repurposing already marketed drugs as adjuvants to chemotherapy. Accordingly, we have previously developed the combination of docetaxel and the cholesterol-lowering drug, lovastatin, as a powerful trigger of HGT-1 human GC cells’ apoptosis using 2D cultures. Because 3D models, known as spheroids, are getting recognized as possibly better suited than 2Ds in toxicological research, we aimed to investigate the efficacy of this drug combination with such a model. We established monocellular spheroids from two human (GC) cell lines, HGT-1 and AGS, and bicellular spheroids from these cells mixed with cancer-associated fibroblasts. With these, we surveyed drug-induced cytotoxicity with MTT assays. In addition, we used the Incucyte live imaging and analysis system to follow spheroid growth and apoptosis. Taken together, our results showed that the lovastatin + docetaxel combination was an efficient strategy to eliminate GC cells grown in 2D or 3D cultures, lending further support in favor of repurposing lovastatin as an adjuvant to taxane-based anticancer treatment.
Highlights
Gastric cancer (GC) is the third cause of cancer-related mortality worldwide and is often diagnosed at advanced stages of the disease
Docetaxel and lovastatin are cytotoxic to human gastric cancer HGT‐1 and AGS cells in 2D model
We have shown previously that lovastatin enhanced the apoptosis induction brought about by docetaxel in HGT-1 human gastric cancer cells in 2 D42
Summary
Gastric cancer (GC) is the third cause of cancer-related mortality worldwide and is often diagnosed at advanced stages of the disease This makes the development of more comprehensive models and efficient treatments crucial. Combined treatment is often the basis of current chemotherapy regimen, by which anti-tumor agents show stronger effects[8]. This may extend to drug repurposing as an alternative strategy[9]. A large amount of in vitro and in vivo data have suggested that statins bear anti-tumor activity potential, since they decreased cellular proliferation, inhibited metastasis and induced apoptosis[12–16] including in human breast cancer[17], esophageal carcinoma18, melanoma[19] cells, or breast cancer stem cells[20]. The potential of MCTS in predicting the in vivo efficacy of different chemotherapeutic agents has been clearly evidenced, Scientific Reports | (2022) 12:1488
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
