Neoplasma Vol.53, p.111-118, 2006
|
Title: A disconnect between antitumor and antiangiogenic effects of
fluvastatin in vitro and in vivo
|
Author: H., KLEMENT
; J., RAK
; |
|
Abstract: The possible role of statins in cancer is controversial. Indeed,
among the multiplicity of biological effects ascribed to
these widely used cholesterol lowering agents some could, at least
in theory, inhibit tumor growth (e.g. by inhibiting Ras
oncoproteins), while other actions are inert, or may even
stimulate cancer aggressiveness (e.g. through promoting
neovascularization). In order to address some of these
controversies, we set out to compare the effects of statins on
growth of
cancer and endothelial cells in vitro, to the impact of these
drugs on angiogenesis-dependent expansion of the corresponding
tumors in vivo. Water-soluble fluvastatin was used at
concentrations (0–800 ng/ml) against human umbilical vein
endothelial
cells (HUVEC), and several well-characterized cancer cell lines in
culture, including: carcinoma (LLC), melanoma
(B16F1) and fibrosarcoma driven by mutant H-ras (528ras1).
Endpoints were based on 3H-thymidine incorporation assay,
cell morphology and tumorigenicity in mice. The growth inhibitory
effects of fluvastatin varied among cancer cell lines
(LLC>B16F1>528ras1), irrespectively of their mutant H-ras status.
Fluvastatin also blocked the action of angiogenic factors
on cultured endothelial cells, but was relatively ineffective
against highly angiogenic and aggressive tumors both in
young mice (6–8 weeks), and in less aggressively growing tumors in
aged (80–90 weeks) mice. Thus, antitumor and
antiangiogenic activity of fluvastatin in vitro is not
recapitulated in vivo. Tumors may display a form of resistance to
statins
through a mechanism operative only in vivo.
|
|
Keywords: statins, cancer, angiogenesis, ras, anticancer therapy, endothelium
|
Year: 2006, Volume: 53, Issue: |
Page From: 111, Page To: 118 |
|
|
|
|
download file |
|
|
|
|