Pioglitazone Treatment Increases Survival and Prevents Body Weight Loss in Tumor-Bearing Animals: Possible Anti-Cachectic Effect

Pioglitazone Treatment Increases Survival and Prevents Body Weight Loss in Tumor-Bearing Animals: Possible Anti-Cachectic Effect

Author Beluzi, Mercia Google Scholar
Peres, Sidney B. Google Scholar
Henriques, Felipe S. Google Scholar
Sertie, Rogerio A. L. Google Scholar
Franco, Felipe O. Google Scholar
Santos, Kaltinaitis B. Google Scholar
Knobl, Pamela Google Scholar
Andreotti, Sandra Google Scholar
Shida, Claudio S. Autor UNIFESP Google Scholar
Neves, Rodrigo X. Google Scholar
Farmer, Stephen R. Google Scholar
Seelaender, Marilia Google Scholar
Lima, Fabio B. Google Scholar
Batista, Miguel L. Google Scholar
Institution Univ Mogi das Cruzes
Universidade de São Paulo (USP)
Universidade Estadual de Maringá (UEM)
Universidade Federal de São Paulo (UNIFESP)
Boston Sch Med
Abstract Cachexia is a multifactorial syndrome characterized by profound involuntary weight loss, fat depletion, skeletal muscle wasting, and asthenia; all symptoms are not entirely attributable to inadequate nutritional intake. Adipose tissue and skeletal muscle loss during cancer cachexia development has been described systematically. the former was proposed to precede and be more rapid than the latter, which presents a means for the early detection of cachexia in cancer patients. Recently, pioglitazone (PGZ) was proposed to exhibit anticancer properties, including a reduction in insulin resistance and adipose tissue loss; nevertheless, few studies have evaluated its effect on survival. for greater insight into a potential anti-cachectic effect due to PGZ, 8-week-old male Wistar rats were subcutaneously inoculated with 1 mL (2x10(7)) of Walker 256 tumor cells. the animals were randomly assigned to two experimental groups: TC (tumor + saline-control) and TP5 (tumor + PGZ/5 mg). Body weight, food ingestion and tumor growth were measured at baseline and after removal of tumor on days 7, 14 and 26. Samples from different visceral adipose tissue (AT) depots were collected on days 7 and 14 and stored at -80oC (5 to 7 animals per day/group). the PGZ treatment showed an increase in the survival average of 27.3%(P<0.01) when compared to TC. It was also associated with enhanced body mass preservation (40.7 and 56.3%, p<0.01) on day 14 and 26 compared with the TC group. the treatment also reduced the final tumor mass (53.4%, p<0.05) and anorexia compared with the TC group during late-stage cachexia. the retroperitoneal AT (RPAT) mass was preserved on day 7 compared with the TC group during the same experimental period. Such effect also demonstrates inverse relationship with tumor growth, on day 14. Gene expression of PPAR-gamma, adiponectin, LPL and C/EBP-alpha from cachectic rats was upregulated after PGZ. Glucose uptake from adipocyte cells (RPAT) was entirely re-established due to PGZ treatment. Taken together, the results demonstrate beneficial effects of PGZ treatment at both the early and final stages of cachexia.
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 2010/51078-1
FAPESP: 2008/54091-9
FAPESP: 2012/51094-1
Date 2015-03-25
Published in Plos One. San Francisco: Public Library Science, v. 10, n. 3, 16 p., 2015.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 16
Origin http://dx.doi.org/10.1371/journal.pone.0122660
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000351880000224
URI http://repositorio.unifesp.br/handle/11600/38899

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