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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Nintedanib inhibits growth of human prostate carcinoma cells by modulating both cell cycle and angiogenesis regulators

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Autor(es):
da Silva, Raquel Frenedoso [1, 2] ; Dhar, Deepanshi [2] ; Raina, Komal [2, 3] ; Kumar, Dileep [2] ; Kant, Rama [2] ; Alves Cagnon, Valeria Helena [1] ; Agarwal, Chapla [2, 3] ; Agarwal, Rajesh [2, 3]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Campinas Unicamp, Inst Biol, Dept Struct & Funct Biol, Sao Paulo - Brazil
[2] Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Aurora, CO 80045 - USA
[3] Univ Colorado, Ctr Canc, Anschutz Med Campus, Aurora, CO 80045 - USA
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: SCIENTIFIC REPORTS; v. 8, JUN 22 2018.
Citações Web of Science: 0
Resumo

Prostate cancer (PCa) is the most common malignancy and second leading cause of cancer-related deaths in American men. Proliferating cells have higher need for nutrients and oxygen, triggering angiogenesis that plays a critical role in tumor growth, progression and metastasis. Consequently, immense focus has converged onto inhibitors of angiogenesis in cancer treatment, such as Nintedanib, which has shown exceptional antitumor activity via inhibiting cell proliferation and the resulting tumor growth, primarily due to its combined action on tumor cells, endothelial cells and pericytes. Accordingly, here we assessed both in vitro and in vivo efficacy of Nintedanib in PCa. The results showed that Nintedanib decreased cell viability in both androgen dependent- and -independent PCa cells, together with a decrease in cell motility and invasiveness. Nintedanib also reduced the expression of significant genes responsible for cell cycle progression. PCa PC3 xenograft-carrying nude mice treated with Nintedanib showed significantly decreased tumor volume and cell proliferation alongside diminished levels of pro-angiogenic molecules and blood vessel densities. In conclusion, we report that Nintedanib has strong efficacy against PCa in pre-clinical models via modulation of various pathways, and that it could be employed as a promising new strategy to manage PCa clinically. (AU)

Processo FAPESP: 16/13913-2 - Mecanismo molecular com base em Nintedanibe na terapia do câncer da próstata
Beneficiário:Raquel Frenedoso da Silva
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Doutorado