siRNA-mediated silencing of Nanog reduces stemness properties and increases the sensitivity of HepG2 cells to cisplatin.
AC133 Antigen
/ genetics
Biomarkers, Tumor
/ genetics
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Cisplatin
/ pharmacology
Down-Regulation
Drug Resistance, Neoplasm
/ drug effects
Drug Synergism
Gene Expression Regulation, Neoplastic
/ drug effects
Gene Silencing
Hep G2 Cells
Humans
Hyaluronan Receptors
/ genetics
Liver Neoplasms
/ drug therapy
Nanog Homeobox Protein
/ antagonists & inhibitors
Neoplastic Stem Cells
/ chemistry
RNA, Small Interfering
/ pharmacology
SOXB1 Transcription Factors
/ genetics
Cisplatin
Combination therapy
Liver cancer
Nanog siRNA
Journal
Gene
ISSN: 1879-0038
Titre abrégé: Gene
Pays: Netherlands
ID NLM: 7706761
Informations de publication
Date de publication:
05 May 2022
05 May 2022
Historique:
received:
09
11
2021
revised:
27
01
2022
accepted:
11
02
2022
pubmed:
20
2
2022
medline:
19
3
2022
entrez:
19
2
2022
Statut:
ppublish
Résumé
Liver cancer is one of the most lethal cancers having worldwide prevalence. Despite significant progress in cancer therapy, liver cancer-induced mortality is very high. Nanog, as an essential transcription factor modulating cellular multipotency, causes tumor progression, drug resistance, and preserves stemness properties in various tumors such as liver cancer. Thus, this research was conducted to evaluate the impact of combination therapy of Nanog siRNA/cisplatin on the sensitivity of liver cancer cells to this drug. HepG2 cells were transfected with Nanog siRNA and treated with cisplatin, individually and in combination. Then, it was observed that in transfected HepG2 cells, Nanog expression was significantly reduced at mRNA level and also these cells were sensitized to cisplatin. In addition, to assess the impact of Nanog siRNA and cisplatin individually and in combination on cells' viability, migration capacity, apoptosis, and cell cycle progression, the MTT, wound healing, colony formation assay, Annexin V/PI staining, and flow cytometry assays were applied on HepG2 cells, respectively. Also, the quantitive Real-Time PCR was used to check the expression of stemness-associated genes (CD44, CD133, and Sox2), and apoptosis-related genes (caspase-3, 8, 9, BAX and Bcl2) after combination therapy. It is indicated that the combination of Nanog siRNA and cisplatin significantly reduced proliferation, migration, and colony formation ability, as well as increased apoptosis rate, and cell cycle arrest. Also, it is found that the combination of Nanog siRNA and cisplatin down-regulated the expression of stemness-associated genes and up-regulated apoptosis-related genes in HepG2 cells. Hence, it can be suggested that Nanog inhibition in combination with cisplatin is a potential therapeutic strategy for developing new therapeutic approaches for liver cancer.
Identifiants
pubmed: 35182674
pii: S0378-1119(22)00152-4
doi: 10.1016/j.gene.2022.146333
pii:
doi:
Substances chimiques
AC133 Antigen
0
Biomarkers, Tumor
0
CD44 protein, human
0
Hyaluronan Receptors
0
NANOG protein, human
0
Nanog Homeobox Protein
0
PROM1 protein, human
0
RNA, Small Interfering
0
SOX2 protein, human
0
SOXB1 Transcription Factors
0
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
146333Informations de copyright
Copyright © 2022 Elsevier B.V. All rights reserved.