Tanshinone I and simvastatin inhibit melanoma tumour cell growth by regulating poly (ADP ribose) polymerase 1 expression.
Abietanes
/ administration & dosage
Animals
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Cell Cycle
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Drug Synergism
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Melanoma
/ drug therapy
Mice
Poly (ADP-Ribose) Polymerase-1
/ metabolism
Simvastatin
/ administration & dosage
Survival Analysis
Up-Regulation
/ drug effects
Xenograft Model Antitumor Assays
tanshinone I
poly (ADP ribose) polymerase 1
simvastatin
melanoma
veliparib
sunitinib
Journal
Molecular medicine reports
ISSN: 1791-3004
Titre abrégé: Mol Med Rep
Pays: Greece
ID NLM: 101475259
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
03
12
2019
accepted:
03
08
2020
entrez:
12
11
2020
pubmed:
13
11
2020
medline:
20
5
2021
Statut:
ppublish
Résumé
Melanoma is one of the most aggressive forms of skin tumour with poor prognosis; no effective therapy has been established for melanoma at the metastatic stage. The present study aimed to investigate the role of poly (ADP ribose) polymerase (PARP) inhibitors (PARPis) and PARP1 expression in melanoma progression. In addition, whether high PARP1 expression was associated with poor overall survival in melanoma, and whether a combination effect existed between PARPis and other anti‑tumour compounds (e.g., sunitinib) was analysed. The PARP1 expression was detected using western blot analysis and the proliferation of cells was detected with a colony formation assay. In addition, cell viability assays and xenograft tumor experiments were conducted. The results of the present study demonstrated that sunitinib reduced PARP1 expression and proliferation of melanoma cells. Notably, one of the PARPis, veliparib, reversed the inhibitory effect of sunitinib on PARP1 expression and proliferation, indicating that inhibition of PARP1 enzyme activity by PARPi may be different from the inhibition of PARP1 expression in melanoma cell biological function. To further confirm the relationship between PARP1 expression and tumour cell proliferation, seven compounds, including common approved drugs and natural Chinese medicine monomers, were screened, and the results demonstrated that simvastatin and tanshinone I exerted an inhibitory effect on PARP1 expression and melanoma cell proliferation, and their combination was more effective than simvastatin alone <em>in vivo</em>. The results indicated that simvastatin and tanshinone I inhibited melanoma and renal tumour cells by regulating PARP1 expression, and in addition to the enzyme activity of PARP1, the expression of PARP1 protein may serve a role in tumour progression.
Identifiants
pubmed: 33179075
doi: 10.3892/mmr.2020.11678
pmc: PMC7684874
pii: 40
doi:
pii:
Substances chimiques
Abietanes
0
tanshinone
03UUH3J385
Simvastatin
AGG2FN16EV
PARP1 protein, human
EC 2.4.2.30
Poly (ADP-Ribose) Polymerase-1
EC 2.4.2.30
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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