Carcinoma mamário murino 4T1: características morfológicas, imunofenotípicas, bioquímicas e ensaios pré-clínicos com talidomida/ carboplatina

Abstract

4T1 murine mammary carcinoma is a widely used experimental model in the evaluation and better understanding of tumor biology. This is a highly tumorigenic cell line and invasive and metastasis are observed in several organs. This study aims to characterize the morphological, immunophenotypic, biochemical and preclinical trials with thalidomide/ carboplatin in the development of murine 4T1 mammary carcinoma in Balb/c. For this study all animals were inoculated with 2.5 x 106 4T1 mammary carcinoma cells in the left flank (sub-cutaneous). After implantation tumor growth was monitored at different times of development in accordance with the study protocol. Morphologically, the 4T1 murine mammary carcinoma shows malignant epithelial proliferation in solid arrangement with proliferation of pleomorphic cells and high mitotic index. The results suggest that this experimental tumor mitotic index, and the number of apoptotic vessels are directly related to tumor evolution. The results immunohistochemical analysis demonstrated positive for hormone receptors, cytokeratin AE1/AE3, receptors, and markers of cell proliferation of blood vessels. Biochemical tests were also conducted in order to evaluate the role of angiogenic and inflammatory processes in tumor progression. Our results demonstrate that pro-angiogenic cytokines (VEGF), inflammatory (TNF-), macrophages and neutrophils participate actively in the development of murine 4T1 mammary carcinoma, and metastases. Aiming to suggest alternative therapies including greater specificity of antitumor chemotherapeutic agent, low toxicity and possible drug combinations, three trials were proposed. When evaluating the effect of treatment with thalidomide (150 mg/kg/day) on tumor growth in mice 4T1 Balb/c was observed that thalidomide reduces neoplastic growth by controlling neovascularization and recruitment of inflammatory cells in the tumor. Already administration of carboplatin (100mg/kg) was able to reduce by 50% the tumor volume and number of pulmonary metastases, the rate of cell proliferation and vascularization of tumors. Finally, to evaluate the effect of combination thalidomide/ carboplatin in 4T1 tumor growth was observed that this treatment regimen caused greater reduction in tumor size and number of lung metastases as compared to isolated treatments and increased survival of the animals.