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Published on: December 19, 2019
Therapeutic effect of simvastatin on DMBA-induced breast cancer in mice
Behnaz Karimi1, Mahboobeh Ashrafi1, Tahoora Shomali2
1Division of Biochemistry, Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, 713451731, Shiraz, Iran.
Abstract:
Preclinical studies have shown positive effects of statins against specific cancers. This study aimed to determine the therapeutic effect of simvastatin in 12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer. Female albino mice were divided into two groups, with or without DMBA administration. After tumor appearance, DMBA-treated group was further divided into four groups (D1-D4) as control (D1), treated with simvastatin at 80 and 40 mg/kg/day, orally (D2 and D3) and tamoxifen (50 mg/kg/day, orally) treated group (D4). After 4 weeks, animals were sacrificed, serum samples were collected and tumors were dissected for histopathological study and determination of selected parameters. The tumor marker carcinoma antigen 15-3 (CA15-3), oxidative stress parameters and prostaglandin E2 (PGE2) levels were analyzed in serum and tumors in experimental groups. Tamoxifen and high dose of simvastatin improved parameters of mammary carcinogenesis including mean tumor volume, body weight and percent of mortality as compared to mice with breast tumors without treatment (D1). Additionally, simvastatin usage increased total antioxidant capacity (TAC) level, paraoxonase 1 (PON1) activity in serum and decreased total oxidant status (TOS) and malondialdehyde (MDA) levels in tumors similar to tamoxifen. No significant decrease was found in serum CA 15-3 and tumor PGE2 levels in simvastatin and tamoxifen treated groups as compared to D1 group. These data suggest that simvastatin has anticancer effects which are relatively similar to that of tamoxifen in an animal model of breast cancer.
Insights
Simvastatin demonstrated anticancer effects in a breast cancer animal model, improving key health markers and showing antioxidant benefits. Its efficacy was comparable to tamoxifen in this preclinical study.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Preclinical research suggests statins possess anticancer properties.
- Breast cancer remains a significant health concern, necessitating novel therapeutic strategies.
Purpose of the Study:
- To evaluate the therapeutic potential of simvastatin in a 12-dimethylbenz(a)anthracene (DMBA)-induced mouse model of breast cancer.
- To compare simvastatin's effects with tamoxifen, a standard breast cancer treatment.
Main Methods:
- Female albino mice were induced with DMBA to develop breast cancer.
- Tumor-bearing mice were treated with varying doses of simvastatin or tamoxifen.
- Serum and tumor samples were analyzed for tumor markers (CA15-3), oxidative stress (TAC, TOS, MDA), and prostaglandin E2 (PGE2).
Main Results:
- Simvastatin, particularly at a high dose, and tamoxifen improved tumor volume, body weight, and survival rates compared to untreated controls.
- Simvastatin enhanced serum total antioxidant capacity (TAC) and paraoxonase 1 (PON1) activity.
- Simvastatin reduced tumor total oxidant status (TOS) and malondialdehyde (MDA) levels, mirroring tamoxifen's effects.
- No significant changes were observed in serum CA15-3 or tumor PGE2 levels with simvastatin or tamoxifen treatment.
Conclusions:
- Simvastatin exhibits significant anticancer effects in a preclinical breast cancer model.
- The observed benefits of simvastatin include improved antioxidant status and reduced oxidative stress.
- Simvastatin's efficacy in this model is comparable to that of tamoxifen, suggesting its potential as a therapeutic agent.
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