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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Knockdown of NF-kappa B1 by shRNA Inhibits the Growth of Renal Cell Carcinoma In Vitro and In Vivo

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Author(s):
Ikegami, Amanda [1] ; Teixeira, Luiz Felipe S. [1] ; Braga, Marina S. [2] ; Dias, Matheus Henrique Dos S. [3] ; Lopes, Eduardo C. [3] ; Bellini, Maria Helena [1]
Total Authors: 6
Affiliation:
[1] IPEN CNEN SP, Dept Biotechnol, 2242 Av Lineu Prestes, Cidade Univ, BR-05508000 Butanta, SP - Brazil
[2] Univ Sao Paulo, Dept Pharm, Fac Pharmaceut Sci, Sao Paulo - Brazil
[3] Inst Butantan, LETA, Ctr Toxins Immune Response & Cell Signaling CeTIC, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: ONCOLOGY RESEARCH; v. 26, n. 5, p. 743-751, 2018.
Web of Science Citations: 0
Abstract

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-kappa B 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-kappa B in RCC, and many have implicated NF-kappa B1 (p50) as an important molecule in tumor progression and metastasis. In the present study, a lentivirus was used to deliver shRNA targeting NF-kappa B1 into mouse RCC (Renca) cells. It was determined that the knockdown of the NF-kappa B1 gene led to a reduction in cell proliferation and late apoptosis/necrosis in vitro. Flow cytometry analysis demonstrated G(2)/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-kappa B1 cells have significantly diminished tumori genicity. Moreover, immunohistochemical analysis revealed an increase in necrotic areas of Renca-shRNA-NF-kappa B1 tumors. Thus, this study indicates that downregulation of NF-kappa B1 can suppress RCC tumorigenesis by inducing late apoptosis/necrosis. Therefore, NF-kappa B1 may be a potential therapeutic target for RCC. (AU)

FAPESP's process: 14/19265-7 - Functional assessment of NF-Kb1 gene in the tumorigenesis of renal cell carcinoma cell lines
Grantee:Maria Helena Bellini Marumo
Support Opportunities: Regular Research Grants