Propofol induces apoptosis and ameliorates 5‑fluorouracil resistance in OSCC cells by reducing the expression and secretion of amphiregulin.
Amphiregulin
/ chemistry
Antimetabolites, Antineoplastic
/ pharmacology
Apoptosis
Carcinoma, Squamous Cell
/ drug therapy
Cell Proliferation
Drug Resistance, Neoplasm
/ drug effects
Fluorouracil
/ pharmacology
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Hypnotics and Sedatives
/ pharmacology
Mouth Neoplasms
/ drug therapy
Propofol
/ pharmacology
Tumor Cells, Cultured
5‑fluorouracil
amphiregulin
drug resistance
oral squamous cell carcinoma
propofol
secreted protein
Journal
Molecular medicine reports
ISSN: 1791-3004
Titre abrégé: Mol Med Rep
Pays: Greece
ID NLM: 101475259
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
05
08
2021
accepted:
29
09
2021
entrez:
3
12
2021
pubmed:
4
12
2021
medline:
8
3
2022
Statut:
ppublish
Résumé
Among the different types of oral cancer, >90% of cases are oral squamous cell carcinoma (OSCC). 5‑fluorouracil (5‑FU) is a commonly used treatment for OSCC, but cells typically display resistance to the drug. Propofol, an intravenous anesthetic agent, exhibits certain anticancer effects, including the inhibition of cancer cell proliferation, migration and invasion. Secreted proteins, such as growth factors and cytokines are involved in cancer development and progression, but the effect of propofol on secreted proteins in OSCC is not completely understood. An MTT assay, flow cytometry and western blotting were performed to determine the anticancer effects of propofol. The secretion profile of OSCC was determined using an antibody array, and clinical importance was assessed using the Gene Expression Profiling Interactive Analysis database. The results were verified by performing reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting. 5‑FU‑resistant cells were established to determine the role of the gene of interest in drug resistance. The results demonstrated that propofol decreased cell viability and promoted cell apoptosis. The antibody array results showed that propofol attenuated the secretion of multiple growth factors. The bioinformatics results indicated that amphiregulin (AREG) was expressed at significantly higher levels in cancer tissues, which was also related to poor prognosis. The results of RT‑qPCR and western blotting revealed that propofol decreased AREG expression. Pretreatment with exogenous recombinant AREG increased EGFR activation and conferred propofol resistance. Moreover, the results indicated that the expression and activation of AREG was also related to 5‑FU resistance, but propofol ameliorated 5‑FU drug resistance. Therefore, the present study suggested that propofol combination therapy may serve as an effective treatment strategy for OSCC.
Identifiants
pubmed: 34859260
doi: 10.3892/mmr.2021.12552
pii: 36
pmc: PMC8669682
doi:
pii:
Substances chimiques
AREG protein, human
0
Amphiregulin
0
Antimetabolites, Antineoplastic
0
Hypnotics and Sedatives
0
Fluorouracil
U3P01618RT
Propofol
YI7VU623SF
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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