|
|
|
|
|
|
|
|
abstact/open access
Abstract
Objective: Granulosa cell tumors of the ovary (GCTs)
represent a specific subset of malignant ovarian tumors, of which there
are 2 distinct subtypes, the juvenile and the adult form. Aside from
surgery, no reliable therapeutic options currently exist for patients
with GCT. This study sought to investigate the potential role of small
molecule tyrosine kinase inhibitors (TKIs) as novel therapeutics in the
clinical management of GCT.
Materials and Methods:
Using TKI with distinct but overlapping multitargeted specificities,
cellular proliferation, viability, and apoptosis were evaluated in 2
human GCT-derived cell lines, COV434 and KGN.
Results:
Sunitinib, which targets the imatinib-inhibited tyrosine kinases of
VEGFR, KIT, PDGFR, and FLT-3, was without effect in COV434 and KGN cell
lines. Sorafenib, which has a high affinity for RAF1 and BRAF, dose
dependently inhibited cellular proliferation and viability in both cell
lines at concentrations equivalent to that seen in other systems.
A RAF1
kinase inhibitor was without effect, suggesting that sorafenib is
acting via inhibition of BRAF, or that aberrant signaling originates
upstream of BRAF in the MAPK pathway. In the presence of a selective Src
family inhibitor (SU6656), cell proliferation and cell viability
responses dissociated; that is, although SU6656 dose dependently
inhibited cell viability, it had limited effect on proliferation and
apoptosis.
Conclusions: These findings implicate BRAF in the
activated signaling responsible for the growth and viability of GCT and
suggest that TKI already in clinical use may be a therapeutic option in
the treatment of GCT.
0 comments :
Post a Comment
Your comments?
Note: Only a member of this blog may post a comment.