Intratumoral injection of PKR shRNA expressing plasmid inhibits B16-F10 melanoma growth

被引:8
作者
Andre, Nayara Delgado [1 ]
Oliveira Silva, Viviane Aline [2 ]
Ehara Watanabe, Maria Angelica [3 ]
De Lucca, Fernando Luiz [2 ]
机构
[1] Univ Fed Sao Joao del Rei, BR-35501296 Divinopolis, MG, Brazil
[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP, Brazil
[3] Univ Estadual Londrina, Dept Pathol Sci, Ctr Biol Sci, BR-86057970 Londrina, PR, Brazil
基金
巴西圣保罗研究基金会;
关键词
RNAi; PKR; B16-F10; melanoma; intratumoral injection; tumor growth; DEPENDENT PROTEIN-KINASE; I-KAPPA-B; SMALL INTERFERING RNAS; REGULATORY RNA; ACTIVATION; DELIVERY; CANCER; LYMPHOCYTES; POTENTIALS; APOPTOSIS;
D O I
10.3892/or.2014.3410
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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-kappa B. 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.
引用
收藏
页码:2267 / 2273
页数:7
相关论文
共 27 条
[1]   Knockdown of PKR expression by RNAi reduces pulmonary metastatic potential of B16-F10 melanoma cells in mice:: Possible role of NF-κB [J].
Andre, Nayara Delgado ;
De Lucca, Fernando L. .
CANCER LETTERS, 2007, 258 (01) :118-125
[2]   The double-stranded RNA-dependent protein kinase PKR: Structure and function [J].
Clemens, MJ ;
Elia, A .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 1997, 17 (09) :503-524
[3]   Assessment of drug delivery and anticancer potentials of nanoparticles-loaded siRNA targeting STAT3 in lung cancer, in vitro and in vivo [J].
Das, Jayeeta ;
Das, Sreemanti ;
Paul, Avijit ;
Samadder, Asmita ;
Bhattacharyya, Soumya Sundar ;
Khuda-Bukhsh, Anisur Rahman .
TOXICOLOGY LETTERS, 2014, 225 (03) :454-466
[4]   Activation of RNA-dependent protein kinase and nuclear factor-kB by regulatory RNA from lipopolysaccharide-stimulated macrophages: implications for cytokine production [J].
De Lucca, FL ;
Serrano, SV ;
Souza, LR ;
Watanabe, MAE .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2002, 450 (01) :85-89
[5]   Intratumoral delivery of shRNA targeting cyclin D1 attenuates pancreatic cancer growth [J].
Deharvengt, S. J. ;
Gunn, J. R. ;
Pickett, S. B. ;
Korc, M. .
CANCER GENE THERAPY, 2010, 17 (05) :325-333
[6]   Therapeutic potentials of gene silencing by RNA interference: Principles, challenges, and new strategies [J].
Deng, Yan ;
Wang, Chi Chiu ;
Choy, Kwong Wai ;
Du, Quan ;
Chen, Jiao ;
Wang, Qin ;
Li, Lu ;
Chung, Tony Kwok Hung ;
Tang, Tao .
GENE, 2014, 538 (02) :217-227
[7]   Nanoparticles as Drug Delivery Systems in Cancer Medicine: Emphasis on RNAi-Containing Nanoliposomes [J].
Diaz, Monica Rivera ;
Vivas-Mejia, Pablo E. .
PHARMACEUTICALS, 2013, 6 (11) :1361-1380
[8]   RNAi Therapeutic Platforms for Lung Diseases [J].
Fujita, Yu ;
Takeshita, Fumitaka ;
Kuwano, Kazuyoshi ;
Ochiya, Takahiro .
PHARMACEUTICALS, 2013, 6 (02) :223-250
[9]   Down-regulation of signal transducer and activator of transcription 3 expression using vector-based small interfering RNAs suppresses growth of human prostate tumor in vivo [J].
Gao, LF ;
Zhang, L ;
Hu, JD ;
Li, F ;
Shao, YT ;
Zhao, D ;
Kalvakolanu, DV ;
Kopecko, DJ ;
Zhao, XJ ;
Xu, DQ .
CLINICAL CANCER RESEARCH, 2005, 11 (17) :6333-6341
[10]   Impact of protein kinase PKR in cell biology:: from antiviral to antiproliferative action [J].
Garcia, M. A. ;
Gil, J. ;
Ventoso, I. ;
Guerra, S. ;
Domingo, E. ;
Rivas, C. ;
Esteban, M. .
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS, 2006, 70 (04) :1032-+