[In vitro study on inhibition of human choroidal melanoma OCM-1 cell line by arsenic trioxide].
OBJECTIVE
To investigate the effects and mechanisms of arsenic trioxide (ATO) on human choroidal melanoma cell line OCM-1.


METHODS
OCM-1 cells were cultured with 0.75 to 24.00 micromol/L arsenic trioxide for various durations, then cell viability was measured by MTT assay. The cell necrosis and apoptosis rates were observed by flow cytometry. The morphological changes of the cells were examined by electron microscopy. Glutathione peroxidase (GSH-Px) activities were tested. Mitochondrial membrane potential (MMP) was detected by confocal microscopy.


RESULTS
Growth of OCM-1 cells was inhibited by ATO at concentrations of (1.5 to 24.0) micromol/L. However, there was no effect of 0.75 micromol/L ATO on the growth of OCM-1 cells. The inhibition showed both dose and time dependent effects (P < 0.05). The IC(50) was 16.8 micromol/L at 24 h. Flow cytometry analysis showed a positive correlation between the rate of cell necrosis and apoptosis and the concentration of ATO. The cell necrosis rates were higher than the cell apoptosis rates at various concentrations of ATO. OCM-1 cells cultured with ATO showed the classic morphologic characteristics of necrosis and apoptosis. GSH-Px activities and MMP decreased in a dose dependent manner.


CONCLUSIONS
ATO inhibits the growth of OCM-1 cells. The mechanism of this effect is that ATO inhibits the GSH-Px activities, decreases the MMP and impairs mitochondrial energy synthesis, which induces necrosis and apoptosis of human choroidal melanoma COM-1 cells eventually.
Wang
Chun-fang
CF
Beijing Institute of Ophthalmology, Beijing Tongren Ophthalmic Center, Capital University of Medical Sciences, Beijing 100005, China.
Li
Bin
B
Zhang
Hai-yan
HY
Li
Wei-hong
WH
Sun
Yi-lin
YL
Xu
Yan-ling
YL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002830:Choroid Neoplasms / Q000201:enzymology / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000201:enzymology / Q000473:pathology*; D010087:Oxides / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D005979:Glutathione Peroxidase; D000077237:Arsenic Trioxide