Alpha7 nicotinic acetylcholine receptor expression in Sorafenib-resistant Hepatocellular carcinoma cells.
Chemosensitivity
Combination therapy
Hepatocellular carcinoma
Sorafenib
siRNA
α7nAchR
Journal
Medical oncology (Northwood, London, England)
ISSN: 1559-131X
Titre abrégé: Med Oncol
Pays: United States
ID NLM: 9435512
Informations de publication
Date de publication:
16 Aug 2022
16 Aug 2022
Historique:
received:
29
03
2022
accepted:
04
05
2022
entrez:
16
8
2022
pubmed:
17
8
2022
medline:
19
8
2022
Statut:
epublish
Résumé
Hepatocellular carcinoma (HCC), the most prevalent kind of liver cancer, remains one of the world's main causes of death. The alpha7 nicotinic acetylcholine receptor (α7nAchR) has been recognized to be overexpressed in malignancies and chemoresistance. Since little is known about the role of α7nAchR expression in drug-resistant cells, this study was designed to investigate the effect of α7nAchR suppression in combination with Sorafenib (SOR) on SOR-resistant HCC cells. First, SOR-resistant HCC cells were generated. To suppress the expression of α7nAchR, cells were treated with SOR following siRNA transfection. qRT-PCR was used to examine the expression of α7nAchR and apoptotic genes by evaluating the IC50 of SOR and the combination of α7nAchR siRNA and SOR on the survival of resistant cells. Moreover, apoptosis, autophagy, and cell cycle analysis for resistant HCC cells were performed using flow cytometry. Cell migration and colony formation assays were also used for further confirmation. Our results suggest that inhibiting α7nAchR can lead resistant HCC cells to become sensitive. Furthermore, when siRNA and SOR were treated together, HCC-resistant cells showed a considerable reduction in α7nAchR mRNA gene expression. In addition, when α7nAchR was downregulated in combination with SOR, migration and colony formation were inhibited. Apoptosis was triggered by modulating the expression of apoptotic target genes, and cell cycle arrest was observed in the G2-M and subG1 phases. Overexpression of α7nAchR in SOR-resistant HCC cells suggests that it might be a therapeutic target for HCC cell resistance therapy.
Identifiants
pubmed: 35972579
doi: 10.1007/s12032-022-01745-5
pii: 10.1007/s12032-022-01745-5
doi:
Substances chimiques
Chrna7 protein, human
0
RNA, Small Interfering
0
alpha7 Nicotinic Acetylcholine Receptor
0
Sorafenib
9ZOQ3TZI87
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
165Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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