Dados do Resumo

Título

Evaluation of the effects of NT157, a multi-target inhibitor, in pancreatic cancer models

Introdução

Pancreatic cancer, with its high mortality rate, is often diagnosed late due to subtle early symptoms. Although many mechanisms of tumor growth remain elusive, key pathways such as IGF1R, STAT3, and PI3K/AKT are known. NT157 emerges as a promising antineoplastic agent, inhibiting IRS1/2 proteins to regulate PI3K/AKT and disrupting STAT3 activation via protein phosphatase modulation. These effects highlight NT157's potential in effectively targeting tumor growth.

Objetivo

In view of the above, the objective is to analyze the effects of the compound NT157 on the MIA PaCa-2, PANC-1 and AsPC-1 pancreatic cancer cell lines.

Métodos

Cells were treated with vehicle or increasing concentrations of NT157.
The MTT assay was performed, in which cells were cultured in appropriate culture medium supplemented with 10% fetal bovine serum in the presence of vehicle or concentrations of 0.8 to 50 μM for 24, 48 and 72 hours. After the incubation period, 10 μL of a solution containing MTT at 5 mg/mL was added and incubated for 4 hours at 37°C. The reaction was stopped using 150 μL of 0.1N HCl. Cell viability was subsequently measured at absorbance of 570 using an automatic plate reader.
In the colony formation assay, cell lines were distributed in six-well plates in the presence of vehicle or concentrations of 0.4 to 6.4 μM for 12 days. The plates were fixed and stained with a solution of 10% ethanol and 1% crystal violet and the data analyzed with ImageJ software.

Resultados

The use of the drug NT157 proved to be effective against pancreatic cancer. In both cell viability assays, the MIA PaCa-2 cell line showed greater sensitivity to the drug, reaching an IC50 close to 1.4 μM for the 72-h interval. In contrast, the IC50 of both the AsPC-1 and PANC-1 cell lines were higher: 8.9 μM and 9.2 μM, respectively. Furthermore, in the clonogenic assay, from the concentration of 1.6 μM, the average clonal growths of the Mia PaCa-2 and AsPC-1 cell lines compared to the control were 7.62% and 32.31%, in that order. At the concentration of 3.2 μM, the average growth of the PANC-1 cell line was 38.36%.

Conclusões

Our findings indicate that NT157 negatively interferes with cell viability in different pancreatic cancer cell lines.

Financiador do resumo

This study was financed by a fellowships from FAPESP (grants #2023/15950-6).

Palavras Chave

NT157; Pancreatic cancer; Cell signaling pathways