Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines

利用药物组合和胃癌细胞系表征重新利用苯扎托品、纳他霉素和硝唑尼特

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作者:Eduarda Ribeiro, Diana Araújo, Mariana Pereira, Bruna Lopes, Patrícia Sousa, Ana Catarina Sousa, André Coelho, Alexandra Rêma, Rui Alvites, Fátima Faria, Cláudia Oliveira, Beatriz Porto, Ana Colette Maurício, Irina Amorim, Nuno Vale

Abstract

Gastric cancer (GC) ranked as the fifth most incident cancer in 2020 and the third leading cause of cancer mortality. Surgical prevention and radio/chemotherapy are the main approaches used in GC treatment, and there is an urgent need to explore and discover innovative and effective drugs to better treat this disease. A new strategy arises with the use of repurposed drugs. Drug repurposing coupled with drug combination schemes has been gaining interest in the scientific community. The main objective of this project was to evaluate the therapeutic effects of alternative drugs in GC. For that, three GC cell lines (AGS, MKN28, and MKN45) were used and characterized. Cell viability assays were performed with the reference drug 5-fluororacil (5-FU) and three repurposed drugs: natamycin, nitazoxanide, and benztropine. Nitazoxanide displayed the best results, being active in all GC cells. Further, 5-FU and nitazoxanide in combination were tested in MKN28 GC cells, and the results obtained showed that nitazoxanide alone was the most promising drug for GC therapy. This work demonstrated that the repurposing of drugs as single agents has the ability to decrease GC cell viability in a concentration-dependent manner.

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