IFNγ induces apoptosis in gemcitabineresistant pancreatic cancer cells.
Mol Med Rep
; 29(5)2024 05.
Article
em En
| MEDLINE
| ID: mdl-38488034
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent and aggressive form of pancreatic cancer. Gemcitabine (GEM), the firstline treatment for PDAC, which alleviates symptoms and enhances the quality of life of patients. However, it is prone to lead to the development of drug resistance during treatment. Interferon (IFN)γ exhibits antitumor and immunomodulatory properties. The present study aimed to explore the impact of IFNγ on the viability, migration and apoptosis of GEMresistant pancreatic cancer cells. Firstly, a GEMresistant pancreatic cancer cell line, named PANC1/GEM, was constructed. Hematoxylin and eosin staining analyzed the cell morphology, whereas reverse transcriptionquantitative PCR (RTqPCR) assessed the expression levels of the drugresistance genes multidrug resistanceassociated protein (MRP) and breast cancer resistance protein (BCRP). The MTT assay and cell counting techniques were used to determine the appropriate concentration of IFNy and its effects on cell viability. The IFNγinduced apoptosis of PANC1/GEM cells was assessed using an Apoptosis Detection Kit, whereas the impact of IFNγ on the migration of these cells was evaluated using a woundhealing assay. The MTT assay revealed a resistance index of 22.4 in the PANC1/GEM cell line. RTqPCR indicated that, compared with in wildtype cells, the PANC1/GEM resistant strain exhibited lower MRP and higher BCRP mRNA expression levels. The optimal concentration of IFNγ for affecting PANC1/GEM cells was determined to be 0.3 µg/ml. At this concentration, IFNγ induced PANC1/GEM cell apoptosis, along with a notable reduction in migration. Following treatment of PANC1/GEM cells with IFNγ, MRP expression increased whereas BCRP mRNA expression decreased, indicating a reversal in their drugresistance gene expression. In conclusion, IFNγ exhibited antitumor immune properties by upregulating MRP and downregulating BCRP expression, reversing drugresistance gene expression, and reducing cell viability and migration, while promoting apoptosis in PANC1/GEM cells. IFNγ could potentially serve as a treatment option for patients with GEMresistant pancreatic cancer.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Carcinoma Ductal Pancreático
Limite:
Humans
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2024
Tipo de documento:
Article