Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0027627 (
metastases
)
103,950
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Uveal melanoma (UM) has a high mortality rate due to liver metastasis. The insulin-like growth factor-1 receptor (IGF-1R) is highly expressed in UM and has been shown to be associated with hepatic
metastases
. Targeting IGF signalling may be considered as a promising approach to inhibit the process of metastatic UM cells.
Pristimerin
(
PRI
) has been demonstrated to inhibit the growth of several cancer cells, but its role and underlying mechanisms in the IGF-1-induced UM cell proliferation are largely unknown. The present study examined the anti-proliferative effect of
PRI
on UM cells and its possible role in IGF-1R signalling transduction. MTT and clonogenic assays were used to determine the role of
PRI
in the proliferation of UM cells. Flow cytometry was performed to detect the effect of
PRI
on the cell cycle distribution of UM cells. Western blotting was carried out to assess the effects of
PRI
and IGF-1 on the IGF-1R phosphorylation and its downstream targets. The results indicated that IGF-1 promoted the UM cell proliferation and improved the level of IGF-1R phosphorylation, whereas
PRI
attenuated the effect of IGF-1. Interestingly,
PRI
could not only induce the G1 phase accumulation and reduce the G2 phase induced by IGF-1, but also could stimulate the expression of p21 and inhibit the expression of cyclin D1. Besides,
PRI
could attenuate the phosphorylations of Akt, mTOR and ERK1/2 induced by IGF-1. Furthermore, the molecular docking study also demonstrated that
PRI
had potential inhibitory effects on IGF-1R. Taken together, these results indicated that
PRI
could inhibit the proliferation of UM cells through down-regulation of phosphorylated IGF-1R and its downstream signalling.
...
PMID:Pristimerin attenuates cell proliferation of uveal melanoma cells by inhibiting insulin-like growth factor-1 receptor and its downstream pathways. 3150 90
