Chemopreventive effect of omega-3 polyunsaturated fatty acids and atorvastatin in rats with bladder cancer

Abstract

Bladder cancer remains a huge concern for the medical community because of its incidence and prevalence rates, as well as high percentage of recurrence and progression. Omega-3 polyunsaturated fatty acids and atorvastatin proved anti-inflammatory effects through peroxisome proliferator-activated receptor gamma mechanism. However, their chemopreventive effect still remained to be examined and clarified. In this study, bladder cancer was induced in rats by the chemical carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine. Omega-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid: 2:3 w/w; 1200 mg/kg) and/or atorvastatin (6 mg/kg) were given orally daily to rats for eight consecutive weeks concomitantly with N-butyl-N-(4-hydroxybutyl)nitrosamine and continued for further 4 weeks after cessation of N-butyl-N-(4-hydroxybutyl)nitrosamine administration. The histopathological examination of rat bladder revealed the presence of tumors and the absence of apoptotic bodies in sections from N-butyl-N-(4-hydroxybutyl)nitrosamine group, while tumors were absent and apoptotic bodies were clearly observed in sections from rat groups treated with omega-3 polyunsaturated fatty acids, atorvastatin, or both drugs. The study of the molecular mechanisms illustrated downregulation of COX-2 and P53 (mutant) genes and suppression of transforming growth factor beta-1 and the lipid peroxidation product malondialdehyde in serum of rats of the three treated groups. This chemopreventive effect was confirmed by and associated with lower level of bladder tumor antigen in urine. However, the combined treatment with both drugs exhibited the major protective effect and nearly corrected the dyslipidemia that has been induced by N-butyl-N-(4-hydroxybutyl)nitrosamine. Collectively, omega-3 polyunsaturated fatty acids and atorvastatin, besides having anti-inflammatory properties, proved a chemopreventive effect against bladder cancer, which nominates them to be used as adjuvant therapy with other chemotherapeutics.

Effect of low‐energy shock wave therapy on intravesical epirubicin delivery in a rat model of bladder cancer

“…All rats that did not complete the study period were excluded from the analysis. Similar mortality rates were also reported in previous studies [24,25]. The losses in body weight and bladder/body ratio were significantly lower in the combined treatment group.…”

Preventive effect of pomegranate juice against chemically induced bladder cancer: An experimental study

“…The tumor suppressor TP53 gene controls cell cycle and apoptosis and therefore it plays a critical role in carcinogenesis. Mutation of TP53 gene and subsequent production of dysfunctional p53 protein with prolonged half-life was detected in BBN administrated rats ( El-Ashmawy et al., 2017 ). Intake of PJ in our study reduced expression of mutant TP53 gene among cancer-prevented group, therefore supporting the apoptotic and anticancer effects of PJ.…”

Targeting EGFR in Combination with Nutritional Supplements on Antitumor Efficacy in a Lung Cancer Mouse Model

“…Recent studies report that the blockade of TGF-β/TβR, Wnt/β-catenin, and AXL/Gas6 signaling can potentially reduce the EGFR-TKI resistance in lung cancer A549, HCC827, and PC9 cell lines [3,4,11]. Treatments with FO result in a significant reduction in the serum levels of TGF-β in the bladder cancer model [32]. The combination treatment with FO and Se suppresses AXL expression in HCC827 lung adenocarcinoma cells [19], although few studies show either FO or Se modulates AXL/Gas6 expression in cancer cells.…”