Knockdown of NF-κB1 by shRNA inhibits the growth of renal cell carcinoma in vitro and in vivo

IKEGAMI, AMANDATEIXEIRA, LUIZ F.S.BRAGA, MARINA S.DIAS, MATHEUS H. dos S.LOPES, EDUARDO C.BELLINI, MARIA H.2018-02-202018-02-202018IKEGAMI, AMANDA; TEIXEIRA, LUIZ F.S.; BRAGA, MARINA S.; DIAS, MATHEUS H. dos S.; LOPES, EDUARDO C.; BELLINI, MARIA H. Knockdown of NF-κB1 by shRNA inhibits the growth of renal cell carcinoma in vitro and in vivo. <b>Oncology Research</b>, v. 26, n. 5, p. 743-751, 2018. DOI: <a href="https://dx.doi.org/10.3727/096504017X15120379906339">10.3727/096504017X15120379906339</a>. Disponível em: http://repositorio.ipen.br/handle/123456789/28516.0965-0407http://repositorio.ipen.br/handle/123456789/28516Renal 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.743-751openAccesskidneyscarcinomascell culturescell proliferationrnaimmunityKnockdown of NF-κB1 by shRNA inhibits the growth of renal cell carcinoma in vitro and in vivoArtigo de periódico52610.3727/096504017X15120379906339https://orcid.org/0000-0003-2852-618973.2656.00