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Abstract Title:

Antitumor effectiveness of a combined therapy with a new cucurbitacin B derivative and paclitaxel on a human lung cancer xenograft model.

Abstract Source:

Toxicol Appl Pharmacol. 2017 Jun 10 ;329:272-281. Epub 2017 Jun 10. PMID: 28610991

Abstract Author(s):

Lucas Lourenço Marostica, André Luís Branco de Barros, Juliana Oliveira, Breno Souza Salgado, Geovanni Dantas Cassali, Elaine Amaral Leite, Valbert Nascimento Cardoso, Karen Luise Lang, Miguel Soriano Balparda Caro, Fernando Javier Durán, Eloir Paulo Schenkel, Mônica Cristina de Oliveira, Cláudia Maria Oliveira Simões

Article Affiliation:

Lucas Lourenço Marostica

Abstract:

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors, with a high mortality rate due to the elevated risk of resistance. Natural cucurbitacins and their derivatives are recognized as promising antitumor compounds for several types of cancer, including NSCLC. In a recent study published by our research group, DACE (2-deoxy-2-amine-cucurbitacin E), which is a semisynthetic derivative of cucurbitacin B, showed potential in vitro synergistic antiproliferative effects combined with paclitaxel (PTX) in A549 cells. In sequence, the purpose of this study was to evaluate the in vivo antitumor efficacy of this combined therapy as well as with these drugs individually, using a human NSCLC xenograft model. Some indicators of sub chronic toxicity that could be affected by treatments were also assessed. The results obtained in vivo with the combined treatment (1mg/kg+PTX 10mg/kg) showed the most effective reduction of the relative tumor volume and the highest inhibition of tumor growth and proliferation, when compared with those of the single treatments. Furthermore, scintigraphic images, obtained before and after the treatments, showed that the most effective protocol able to reduce the residual viable tumor mass was the combined treatment. All treatment regimens were well tolerated without significant changes in body weight and no histological and functional damage to liver and kidney tissues. These results corroborate our previous in vitro synergistic effects published. Taken together, these insights are novel and highlight the therapeutic potential of DACE and PTX combination scheme for NSCLC.

Study Type : In Vitro Study

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