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Rosiglitazone shows partial oncostatic effect in rat mammary carcinogenesis
B Bojkova1, K Kajo, M Garajova
1Department of Animal Physiology, P.J Safarik University, Kosice, Slovak Republic. bianka.bojkova@upjs.sk
Abstract:
Peroral antidiabetics from thiazolidinedione (glitazone) group showed oncostatic effects in preclinical models. This study evaluated chemopreventive effects of rosiglitazone in N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats. N-methyl-N-nitrosourea was administered in two intraperitoneal doses each per 50 mg/kg b.w. between 40th and 51st postnatal days. Rosiglitazone was administered in a diet at a concentration of 10 ppm and 100 ppm, respectively, 9 days before the first carcinogen dose until the termination of the experiment. During the experiment the animals were weekly weighed and palpated for the presence of mammary tumors and estimation of latency period, tumor frequency per group and animal, and tumor volume were recorded. The experiment was terminated 16 weeks after the first carcinogen dose, basic tumor growth parameters and selected metabolic and hormonal variables were evaluated. Chemoprevention with higher rosiglitazone dose decreased tumor frequency per group by 44%, other tumor parameters (incidence, tumor frequency per animal) were decreased insignificantly (at both doses), latency period was not changed. Rosiglitazone administration decreased cumulative tumor volume, more efficiently at lower dose. Glycaemia and insulinaemia decreased after lower rosigitazone dose administration but glycaemia did not exceed normal values. Higher rosiglitazone dose alleviated some metabolic alterations resulting from cancer progression more effectively but induced a prominent cardiac hypertrophy.
Insights
Rosiglitazone, a diabetes drug, showed chemopreventive effects against mammary cancer in rats by reducing tumor frequency and volume. However, higher doses induced cardiac hypertrophy, indicating a potential side effect.
Area of Science:
- Oncology
- Pharmacology
- Endocrinology
Background:
- Thiazolidinedione antidiabetics exhibit preclinical oncostatic properties.
- N-methyl-N-nitrosourea (NMU) is a known carcinogen used to induce mammary tumors in rat models.
Purpose of the Study:
- To evaluate the chemopreventive potential of rosiglitazone in NMU-induced rat mammary carcinogenesis.
- To assess the impact of rosiglitazone on tumor growth, latency, and metabolic parameters.
Main Methods:
- Rats were administered NMU to induce mammary carcinogenesis.
- Rosiglitazone was administered orally at 10 ppm and 100 ppm starting 9 days before NMU exposure.
- Tumor parameters, body weight, and metabolic/hormonal variables were monitored over 16 weeks.
Main Results:
- The higher rosiglitazone dose (100 ppm) reduced tumor frequency per group by 44%.
- Both doses decreased cumulative tumor volume, with greater efficacy at the lower dose (10 ppm).
- Lower dose reduced glycemia and insulinemia; higher dose alleviated metabolic alterations but caused cardiac hypertrophy.
Conclusions:
- Rosiglitazone demonstrates chemopreventive effects in a rat mammary cancer model, particularly at lower doses.
- The drug influences tumor growth and metabolic parameters, but potential cardiac side effects warrant consideration.
