Atorvastatin Augments Gemcitabine-Mediated Anti-Cancer Effects by Inhibiting Yes-Associated Protein in Human Cholangiocarcinoma Cells.
Animals
Anticholesteremic Agents
/ administration & dosage
Antimetabolites, Antineoplastic
/ administration & dosage
Apoptosis
/ drug effects
Atorvastatin
/ administration & dosage
Bile Duct Neoplasms
/ drug therapy
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cholangiocarcinoma
/ drug therapy
Connective Tissue Growth Factor
/ genetics
Contractile Proteins
/ genetics
Cysteine-Rich Protein 61
/ genetics
Deoxycytidine
/ administration & dosage
Drug Combinations
Drug Interactions
Humans
Intercellular Signaling Peptides and Proteins
/ genetics
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Muscle Proteins
/ genetics
Myeloid Cell Leukemia Sequence 1 Protein
/ genetics
Nuclear Proteins
/ genetics
Proto-Oncogene Proteins c-bcl-2
/ genetics
Proto-Oncogene Proteins c-yes
/ metabolism
Repressor Proteins
/ genetics
Gemcitabine
HMG-CoA reductase
TEAD transcriptional activation
atorvastatin
cholangiocarcinoma
gemcitabine
yes-associated protein
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
14 Oct 2020
14 Oct 2020
Historique:
received:
10
08
2020
revised:
05
10
2020
accepted:
11
10
2020
entrez:
17
10
2020
pubmed:
18
10
2020
medline:
26
2
2021
Statut:
epublish
Résumé
Cholangiocarcinoma (CCA) is associated with high mortality rates because of its resistance to conventional gemcitabine-based chemotherapy. Hydroxy-methyl-glutaryl-coenzyme A reductase inhibitors (statins) reportedly exert anti-cancer effects in CCA and lower the risk of CCA; however, the underlying mechanism of these effects remains unclear. The proliferative and oncogenic activities of the transcriptional co-activator Yes-associated protein (YAP) are driven by its association with the TEA domain (TEAD) of transcription factors; thereby, upregulating genes that promote cell growth, inhibit apoptosis, and confer chemoresistance. This study investigated the effects of atorvastatin in combination with gemcitabine on the progression of human CCA associated with YAP oncogenic regulation. Both atorvastatin and gemcitabine concentration-dependently suppressed the proliferation of HuCCT-1 and KKU-M213 human CCA cells. Moreover, both agents induced cellular apoptosis by upregulating the pro-apoptotic marker
Identifiants
pubmed: 33066548
pii: ijms21207588
doi: 10.3390/ijms21207588
pmc: PMC7589854
pii:
doi:
Substances chimiques
Ankrd1 protein, mouse
0
Anticholesteremic Agents
0
Antimetabolites, Antineoplastic
0
BCL2 protein, human
0
CCN1 protein, human
0
CCN2 protein, human
0
Contractile Proteins
0
Cysteine-Rich Protein 61
0
Drug Combinations
0
Intercellular Signaling Peptides and Proteins
0
MCL1 protein, human
0
MFAP5 protein, human
0
Muscle Proteins
0
Myeloid Cell Leukemia Sequence 1 Protein
0
Nuclear Proteins
0
Proto-Oncogene Proteins c-bcl-2
0
Repressor Proteins
0
Deoxycytidine
0W860991D6
Connective Tissue Growth Factor
139568-91-5
Atorvastatin
A0JWA85V8F
Proto-Oncogene Proteins c-yes
EC 2.7.10.2
YES1 protein, human
EC 2.7.10.2
Gemcitabine
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Références
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