Silencing of IGHG1 reverses the resistance of pancreatic cancer to multidrug chemotherapy by modulating autophagy.
Environ Toxicol
; 38(8): 1835-1845, 2023 Aug.
Article
em En
| MEDLINE
| ID: mdl-37186415
ABSTRACT
BACKGROUND:
Pancreatic cancer is one of the most aggressive tumors with a high-mortality rate. First-line drugs include 5-fluorouracil (5-FU), gemcitabine (GEM), and oxaliplatin (OXA). Resistance to 5-FU, GEM, and OXA is a major challenge. Immunoglobulin heavy chain F1 (IGHG1) participates in the regulation of cancer progression. It is still unclear how IGHG1 affects 5-FU, GEM, and OXA in pancreatic cancer.METHODS:
The expression status of IGHG1 in pancreatic cancer was analyzed through bioinformatics tools. IGHG1 expression in pancreatic cancer tissues and cells was determined via RT-qPCR. Cell counting kit 8 assays, and flow cytometry analysis were utilized to detect the impact of IGHG1,5-FU, GEM, and OXA on cell proliferation and apoptosis. Western blotting was utilized to detect changes in the levels of the autophagy-associated proteins LC3, Beclin-1, p62, and ATG5. Immunofluorescence assays were employed to determine LC3 expression in cells. Xenograft experiments were conducted on nude mice to study tumor growth.RESULTS:
IGHG1 was overexpressed in pancreatic cancer cells and tissues. IGHG1 expression was downregulated by 5-FU, GEM, or OXA treatment in cells. Treatment with 5-FU, GEM, or OXA repressed viability and promoted apoptosis and autophagy in pancreatic cancer cells. IGHG1 silencing exhibited the same results. Furthermore, IGHG1 depletion notably strengthened the effects of 5-FU, GEM, and OXA on pancreatic cancer cell viability, apoptosis, and autophagy. The combination of IGHG1 depletion with 5-FU, GEM, or OXA significantly reduced tumor growth in vivo.CONCLUSION:
Silencing of IGHG1 could enhance 5-FU, GEM, or OXA function in pancreatic cancer and reverse resistance by regulating apoptosis and autophagy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Desoxicitidina
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Environ Toxicol
Assunto da revista:
SAUDE AMBIENTAL
/
TOXICOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China