Banca de DEFESA: TAMARA JAROSI HANDAJEVSKY
Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.DISCENTE : TAMARA JAROSI HANDAJEVSKY
DATA : 16/06/2021
HORA: 14:00
LOCAL: Por participação remota
TÍTULO:
STUDY OF THE EFFECTS OF METFORMIN ON SURVIVAL, PROLIFERATIVE RATE AND SENSITIVITY OF LEUKEMIC CELLS TO ANTINEOPLASTIC AGENTS
PÁGINAS: 143
GRANDE ÁREA: Ciências Biológicas
ÁREA: Bioquímica
SUBÁREA: Metabolismo e Bioenergética
RESUMO:
Chronic myeloid leukemia (CML) kills about 7.000 Brazilians every year, having seen an overall increase in the incidence of cases from 31.752 in 1990 to 34.179 in 2017. Metformin, a drug prescribed in the treatment of type II diabetes, has called for attention as a potential antitumor agent. Studies show that, among other effects, metformin inhibits the proliferation of cancer cell lines and the metastatic process. In the present project, we describe the effects of metformin on the survival and proliferation of FEPS, a CML cell line with a multiple drug resistance phenotype (MDR). First, we evaluate the evolution of the proliferation of the culture over time and measure the time for doubling FEPS, obtaining a value of 29 ∓ 4 hours. Then, the effects of metformin on FEPS viability were evaluated in cells exposed to the drug (1 - 60 mM) for up to 72 hours using the trypan blue exclusion and MTT reduction assays. The results obtained showed that metformin reduces the viability of FEPS in a concentration and time dependent manner. Although 24 hours of treatment did not significantly reduce viability, even at the highest concentration used, exposure to the drug for 48 hours and 72 hours resulted in IC50 values of 60 mM and 20 mM, respectively. In the proliferation analysis, FEPS cells were evaluated by staining with trypan blue dye with the aid of Countess I equipment, after exposure to the drug (1 - 60 mM) for a period of 120 hours and the viability estimated in cells per mL. The results obtained showed that for concentrations up to 5 mM the proliferative rate of the cells was reduced while in the highest concentrations there was no proliferation (cytostatic effect) or the proliferative rate was lower than the percentage of cell death (cytotoxic effect). Staining the nuclei with propidium iodide and evaluating the progression of the cell cycle using flow cytometry showed that, after treatment of cells with metformin for 48 hours, the percentage of cells in phase S and sub-G1 increased in treatments with metformin in the largest concentrations (40 and 60 mM). After 72 hours of treatment, the same was verified for treatments with metformin at concentrations 5 and 20 mM. In this way, we can conclude that metformin reduces the viability of FEPS cells through a cytostatic manner, inhibiting the progression of the cell cycle in the S phase, and cytotoxic depending on the concentration and time of treatment.
MEMBROS DA BANCA:
Presidente - Interno ao Programa - 1672728 - ANA CAROLINA SANTOS DE SOUZA GALVAO
Membro Titular - Examinador(a) Interno ao Programa - 2605490 - SERGIO DAISHI SASAKI
Membro Titular - Examinador(a) Externo à Instituição - LUCIANA MARIA DE HOLLANDA
Membro Suplente - Examinador(a) Interno ao Programa - 1640114 - MARCELA SORELLI CARNEIRO RAMOS
Membro Suplente - Examinador(a) Interno ao Programa - 2605420 - MARIA CRISTINA CARLAN DA SILVA