Abstract
To investigate the anti-carcinogenic effects of Atorvastatin (Atorva) on a rat bladder carcinogenesis model with N-butyl-N-(4-hydroxibutil)nitrosamine (BBN), four male Wistar rat groups were studied: (1) Control: vehicle; (2) Atorva: 3 mg/kg bw/day; (3) Carcinogen: BBN (0.05%); (4) Preventive Atorva: 3 mg/kg bw/day Atorva + BBN. A two phase protocol was used, in which the drug and the carcinogen were given between week 1 and 8 and tumor development or chemoprevention were expressed between week 9 and 20, when the bladders were collected for macroscopic, histological and immunohistochemical (p53, ki67, CD31) evaluation. Serum was assessed for markers of inflammation, proliferation and redox status. The incidence of bladder carcinoma was: control 0/8 (0%); Atorva 0/8 (0%); BBN 13/20 (65%) and Atorva + BBN 1/8 (12.5%). The number and volume of tumors were significantly lower in the Atorva + BBN group, with a marked reduction in hyperplasia, dysplasia and carcinoma in situ lesions. An anti-proliferative, anti-inflammatory and antioxidant profile was also observed in the preventive Atorva group. p53 and ki67 immunostaining were significantly increased in the BBN-treated rats, which was prevented in the Atorva + BBN group. No differences were found for CD31 expression. In conclusion, Atorvastatin had a clear inhibitory effect on bladder cancer development, probably due to its antioxidant, anti-proliferative and anti-inflammatory properties.
Highlights
In developed nations, bladder cancer is the fourth most common tumor in men and the eighth in women, accounting for 5–10% of all malignancies in men [1]
No relevant changes were detected between the groups throughout the study concerning body weight and beverage consumption
We found in the BBN + Atorva animals a tumour incidence of 12.5% (1 in 8 rats) with a mean tumor volume per tumor of 2.3 ± 0.2 mm3, contrasting with the data from the BBN rats: 65% incidence and 112.5 ± 6.4 mm3 mean tumor volume
Summary
Bladder cancer is the fourth most common tumor in men and the eighth in women, accounting for 5–10% of all malignancies in men [1]. It is associated with high incidence and prevalence rates, and elevated socioeconomic costs [2,3]. Despite current efforts on earlier diagnosis and more aggressive treatments, mortality rates in muscle-invasive disease are still very high [5] In this context, preventive strategies will be pivotal for the management and treatment of bladder cancer, which depends on a better elucidation of the molecular mechanisms underlying appearance and growth. Bladder tumor is associated with exogenous risk factors, which include mainly the cigarette smoking habit, present in more than 50% of the cases in the male population [3,6], and the exposure to occupational carcinogens, in particular aromatic amines and polycyclic aromatic hydrocarbons [6,7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
