Análise in vitro do potencial antitumoral do conjugado LDE/Paclitaxel comparado à formulação do comercial Taxol sobre linhagem celular C6 de glioblastoma de rato

Abstract

Glioblastoma, also known as grade IV astrocytoma, is one of the most common and aggressive types of tumors in the central nervous system. Among the characteristics of this type of tumor, the following stand out: infiltration of isolated tumor cells in normal brain tissue, cell proliferation, angiogenesis and intense necrosis. Currently, the main therapeutic approach consists of surgical resection followed by radiotherapy and chemotherapy. However, in most cases, the tumor is not well defined, spreading through the brain region, which makes it difficult to fully resection. In addition, the removal of tissue from this region can leave several sequels. Consequently, patients have high rates of recurrence and low rates of survival. Another problem in the treatment of this type of tumor is due to the lining of the blood-brain barrier that restricts the entry of molecules and substances, including drugs. Thus, this project aims to analyze the antineoplastic effects of the association of a nanoparticle called LDE with a structure similar to low-density lipoprotein (LDL) that will act as a carrier of the drug paclitaxel (PTX), commercially known as Taxol®, it is a chemotherapeutic drug whose cell antiproliferative action has been proven in the treatment of other types of cancer, such as breast and refractory ovarian cancers. For this purpose, the mouse glioblastoma cell line C6 was used for performing in vitro analysis regarding the effects of these treatments on aspects of viability, cytotoxicity and cell death by apoptosis, using the ApoTox-GloTM Triplex Assay kit (Promega Corporation), which performs the three previously mentioned analyses, sequentially. To evaluate growth and drug effect on PTX and LDE/PTX treatment groups, approximately 1x106 cells were cultured in 96-well microplates at concentrations of 0.01; 0.1; 1 and 10 μM in the times of 24h, 48h and 72h. The control was not exposed to the compounds, containing only DMEM culture medium. Results obtained after treatments with PTX and LDE/PTX were expressed as mean ± standard deviation and analyzed by one-way (cytotoxicity) and two-way (viability and apoptosis) ANOVA, followed by Tukey's post hoc test. Differences were considered significant when p ˂ 0.05.