Chemopreventive Efficacy of Atorvastatin against Nitrosamine-Induced Rat Bladder Cancer: Antioxidant, Anti-Proliferative and Anti-Inflammatory Properties

International Journal of Molecular Sciences

Belmiro Parada³  Flávio Reis¹  Ângela Pinto³  José Sereno³  Maria Xavier-Cunha⁵  Paula Neto⁵  Petronila Rocha-Pereira²  Alfredo Mota⁴  Arnaldo Figueiredo⁴ 

[1] Research Centre for Health Sciences, Beira Interior University, Covilhã, 6201-506, Portugal; E-Mail:;Laboratory of Pharmacology & Experimental Therapeutics, Institute of Biomedical Research on Light and Image, Medicine Faculty, Coimbra University, Coimbra, 3000-548, Portugal; E-Mails:;Department of Urology & Renal Transplantation, Coimbra University Hospital, Coimbra, 3000-075, Portugal; E-Mails:;Service of Anatomic Pathology, Coimbra University Hospital, Coimbra, 3000-075, Portugal; E-Mails:

关键词: bladder cancer;    chemoprevention;    atorvastatin;    antioxidant;    anti-proliferative;    anti-inflammatory;   

DOI  :  10.3390/ijms13078482

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.