Dicycloplatin differentially inhibits proliferation of human aortic smooth muscle and endothelial cells: potential for use in drug-eluting stents.
- Author:
Lian-jun XU
1
;
Run-lin GAO
;
Chao WU
;
Jue YE
;
Li SONG
;
Xin QIAN
Author Information
- Publication Type:Journal Article
- MeSH: Aorta; cytology; Blotting, Western; Cell Proliferation; drug effects; Drug Combinations; Drug-Eluting Stents; Endothelial Cells; cytology; drug effects; Flow Cytometry; Glutamates; pharmacology; Humans; Muscle, Smooth, Vascular; cytology; drug effects; Organoplatinum Compounds; pharmacology; Sirolimus; pharmacology
- From: Chinese Medical Journal 2012;125(24):4386-4392
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDDicycloplatin is a relatively safe third generation platinum-complex anti-cancer drug. The present study focused on the effects of dicycloplatin on in vitro proliferation and apoptosis of human aortic smooth muscle cells (HASMC) and human aortic endothelial cells (HAEC).
METHODSProliferation of HASMC and HAEC, DNA content, and cellular levels of proliferation- and apoptosis-related proteins were assessed using the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay, flow cytometry and Western blotting assays, respectively.
RESULTSDicycloplatin at 10 ng/ml significantly inhibited HASMC proliferation, however, 10 µg/ml were required to significantly inhibit HAEC proliferation. Cell cycle analysis showed that dicycloplatin was a non-specific inhibitor of the cell cycle. Although dicycloplatin significantly decreased proliferating cell nuclear antigen (PCNA) expression in HASMC at all concentrations tested, it did not significantly affect PCNA expression in HAEC; Bax and p53 protein expression was upregulated in dicycloplatin groups.
CONCLUSIONSDicycloplatin at nanogram concentrations significantly inhibits HASMC proliferation, although the effect is relatively weaker than that of sirolimus. In contrast, the effect of dicycloplatin on inhibition of HAEC proliferation is much less pronounced than that on HASMC. The latter characteristics point to the potential for use of dicycloplatin in drug-eluting stents.