Dados do Resumo

Título

The combination of GSK3β and BCL-2 inhibitors in acute myeloid leukemia HL-60 cell line

Introdução

The main treatment for acute myeloid leukemia (AML) is chemotherapy (anthracycline with cytarabine), but VENETOCLAX, a BCL-2 inhibitor, has emerged as an attractive option in the last few years. However, a portion of the patients still do not respond to these treatments. In vitro studies have demonstrated the GSK3β inhibition potential anti-leukemic effect.

Objetivo

Our goal is to evaluate whether the BCL-2 inhibitor (VENETOCLAX) combined with the GSK3β inhibitor (BIO) has an anti-leukemic effect in AML HL-60 lineage.

Métodos

We performed the IC50 of both inhibitors with proliferations assays in HL-60. After determining the IC50, we evaluated the proliferation and cell viability with the combined treatment, counting both living and death cells with the Neubauer chamber and trypan blue. Gene expression was analyzed after 6h treatment with both inhibitors isolated or combined. We performed RT-qPCR for GSK3β and BCL-2, and for cell death related genes (BID and BAX).

Resultados

Treatment with BIO 2uM showed an anti-proliferative effect in HL-60, reducing population growth by 34%, in 48h, when compared to the control (DMSO). In contrast, VENETOCLAX 1nM did not show a significant effect in HL-60 lineage after 48h, with differences observed only after 72h of treatment. However, the combined treatment showed promising results, showing a marked reduction of 16% in HL-60 in relation to the control group in 48h. No difference was observed in GSK3β, BCL-2, BID and BAX expression after inhibitors treatment.

Conclusões

We concluded that the combined treatment of VENETOCLAX and BIO enhances the anti-proliferative effect, and increases cell death, although the mechanisms of cell death must be further investigated.

Financiador do resumo

PIBIC/CNPq

Palavras Chave

Acute Myeloid Leukemia (AML); B-Cell Lymphoma-2 Protein (BCL-2); Glycogen Synthase Kinase 3 b (GSK3b)