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PROTECTIVE EFFECT OF MICRORNA 145 ON METASTATIC PROSTATE CANCER - IN VIVO STUDY.
Introdução, Material, Método, Resultados, Discussão e Conclusões
Introduction: Prostate cancer (PC) is the second most common cause of cancer worldwide. The main treatment for patients will metastatic disease is the androgenic deprivation, but most patients develop resistance to androgen blockade. MiRNAs (miR) are small molecules involved in the control of gene expression and their alteration during PC progression has been studied recently, in order to identify new diagnostic and prognostic biomarkers. Most importantly, there is a possibility to use them as therapeutic agents. miR-145 is an important tumor suppressor miR, controlling c-MYC and k-RAS expression. Using an in vivo model of metastatic PC we treated mice with miR-145 systemically, analyzing the levels of microRNA and its target genes c-MYC and k-RAS in the metastatic tissue.
Methods: 13 Balb/c nude mice were inoculated, in the left ventricle, with PC-3M-luc-C6 cells, a bioluminescent lineage of metastatic, castration-resistant PC. In day 21st, when the metastatic disease was well stablished, the treatment (miR-145 and atelocollagen) started. Three doses were applied in the tail or dorsal vein of the penis with an interval of four days. Eight mice were treated and the remaining 5 were used as controls. In vivo images were obtained by IVIS Spectrum and analysis of miR-145 and genes by qRT-PCR.
Results: Animals treated with miR-145 showed a reduction in bone metastasis luminescence compared to the control group (p=0.03). Although not significant, there was a reduction in the expression levels of c-MYC (1,572 ± 1,524 vs 3,135 ± 2,257 – p= 0,0987) and k-RAS (0,0003441 ± 0,0002322 vs 0,002074± 0,002557 – p= 0,1001).
Conclusion: Animals with metastatic PC treated with miR-145 exhibited a slower tumor growth and a reduction in c-MYC and k-RAS expression. These preliminary findings show a potential therapeutic role of miRs in the treatment of tumors.
Prostate cancer, Metastasis, microRNA-145, Target therapy
Câncer de Próstata Metastático
FMUSP - Sao Paulo - Brasil
VANESSA RIBEIRO GUIMARÃES, NAYARA IZABEL VIANA, RUAN PIMENTA, SABRINA THALITA REIS, IRAN SILVA , DENIS REIS MORAIS, JULIANA ALVES CAMARGO , WILLIAM C NAHAS, MIGUEL SROUG, KATIA RAMOS MOREIRA LEITE