title: Intratumoral injection of PKR shRNA expressing plasmid inhibits B16-F10 melanoma growth.
abstract: The RNA-dependent protein kinase (PKR) is a serine/threonine kinase that is involved in the regulation of important cell processes such as apoptosis, signal transduction, cell proliferation and differentiation. However, the role played by PKR in cancer remains controversial. RNA interference (RNAi) has currently become an important technique in understanding gene function. Previously, we showed that PKR shRNA downregulates PKR expression in B16-F10 melanoma cells and reduces the metastatic potential of these tumor cells. In the present study, we examined the effect of the intratumoral injection of PKR shRNA‑expressing plasmid on the growth of B16-F10 melanoma in mice. The results showed that this treatment significantly reduced tumor growth. Thus, these findings suggested that PKR acts as a tumor suppressor, a finding that is consistent with our previous study on the experimental model of metastasis. Moreover, the results suggested that this effect may be mediated by the transcription factor NF-κB. The present study confirmed the hypothesis that the direct administration of RNAi-based therapeutics in the target tumor is a promising approach for overcoming the obstacles of systemic delivery. The results also suggested that the intratumoral injection of PKR shRNA‑expressing vector is a novel therapeutic approach for human solid tumors such as cutaneous melanoma and breast cancer, since PKR is overexpressed in these tumors.
authors.affiliation: Federal University of São João del-Rei, 35501296 Divinópolis, MG, Brazil.
authors.forename: Nayara Delgado
authors.initials: ND
authors.lastname: André
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Viviane Aline Oliveira
authors.initials: VA
authors.lastname: Silva
authors.affiliation: Department of Pathological Sciences, Biological Sciences Center, State University of Londrina, 86057-970 Londrina, PR, Brazil.
authors.forename: Maria Angelica Ehara
authors.initials: MA
authors.lastname: Watanabe
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: Fernando Luiz
authors.initials: FL
authors.lastname: De Lucca
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D034741:RNA, Small Interfering; D019892:eIF-2 Kinase