Coadjuvant therapy in prostatic cancer: cellular and molecular evaluation of inflammatory and angiogenic responses in human tumoral cellular lineages and in initial and late lesions from transgenic model-TRAMP

Abstract

Prostatic cancer is the second-highest type of cancer around of the world. Processes related to pathogenesis and progression of prostatic cancer such as inflammation and angiogenesis are pointed out as being fundamental factors for lesion development, leading to the repetition of tissue damage and regeneration and to glandular microenvironment imbalance. Thus, these processes are important therapeutic targets. Tempol has been shown to be a promising coadjuvant treatment in different cancer types, showing a direct effect on the inflammatory process and cellular oxidative stress and neoangiogenesis. However, there are many queries about the Tempol response on the prostate. The aim of this study is to evaluate theTempol treatment effects on the inflammatory and angiogenic responses of the prostatic microenvironment in vivo and in vitro. To do this, the characterization in vitro of the human tumoral cellular lineage responses (LnCaP, PC3 e PNT1A) in the Tempol treatment will be evaluated by means of cellular viability; western blotting; gene expression (RT-PCR and PCR array); and oxygen and nitrogen reactive species present in the cell culture. Also, the in vivo evaluation of the prostatic ventral and dorsolateral lobes from TRAMP mice will be verified in two cancer progression degrees: first in 8-12 week old mice(early-stage) and secondly in 16-20 week old mice (late-stage), both treated with 50mg/kg Tempol dose daily for 4 weeks. After the end of the treatment, the prostatic ventral and dorsolateral lobes will be processed for histopathological, immuhistochemical, gene expression (RT-PCR), and Western Blotting evaluation. In addition, taking into consideration the target-gene chosen for the analyzed pathways, possible miRNAs will be identified by means of biocomputing tools verifying if there are changes due to the treatment. Then, the profile of the expression of these small tumoral human lineage markers, as well as the prostatic tissue in the TRAMP model will be evaluated. (AU)