AMANDA IKEGAMI
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Artigo IPEN-doc 24344 Knockdown of NF-κB1 by shRNA inhibits the growth of renal cell carcinoma in vitro and in vivo2018 - IKEGAMI, AMANDA; TEIXEIRA, LUIZ F.S.; BRAGA, MARINA S.; DIAS, MATHEUS H. dos S.; LOPES, EDUARDO C.; BELLINI, MARIA H.Renal cell carcinoma (RCC) accounts for approximately 2-3% of human malignancies and is the most aggressive among urologic tumors. Biological heterogeneity, drug resistance and chemotherapy side effects are the biggest obstacles to the effective treatment of RCC. The NF-кB transcription factor is one of several molecules identified to be responsible for the aggressive phenotype of this tumor. In the past decade, several studies have demonstrated the activation of NF-kB in RCC, and many implicated NF- κB1 (p50) as an important molecule in tumor progression and metastasis. In the present study, a lentivirus was used to deliver shRNA targeting NF-κB1 into mouse renal cell carcinoma (Renca) cells. It was determined that the knockdown of the NF-κB1 gene led to a reduction in cell proliferation and late apoptosis/necrosis in vitro. Flow cytometry analysis demonstrated G2/M arrest in the cells. In addition, immunoblotting analysis revealed a significant increase in cyclin B1 and Bax. In vivo experiments showed that Renca-shRNA-NF-кB1 cells have significantly diminished tumorigenicity. Moreover, immunohistochemical analysis revealed an increase in necrotic areas of Renca-shRNANF- кB1 tumors. Thus, this study indicates that downregulation of NF-кB1 can suppress RCC tumorigenesis by inducing late apoptosis/necrosis. Therefore, NF-кB1 may be a potential therapeutic target for RCC.