Isobolographic assessment of the interaction between adriamycin and photodynamic therapy with meso-chlorin e6 monoethylene diamine in human epithelial ovarian carcinoma (OVCAR-3) in vitro.
OBJECTIVE
Considering the differing mechanisms of cytotoxicity produced by adriamycin and the photosensitizer meso-chlorin e6 monoethylene diamine (Mce6) with light, the interaction of these agents in combination on human ovarian epithelial carcinoma (OVCAR-3 in vitro) was evaluated by dose and effect addition isobole analysis.


METHODS
Mitochondrial respiration via the 3-(4,5-dimethyl thiazol-2 yl)-2,5-diphenyl tetrazolium bromide cleavage assay (MTT) and reproductive capacity via the tritiated thymidine incorporation assay (TI) were assessed 72 and 144 hours after exposure to adriamycin, Mce6, and light (650 nm), and to their combinations, in OVCAR-3 cells grown in vitro (20,000 cells per well).


RESULTS
In the majority of assays, reproductive capacity was more sensitive to the drug(s) than was mitochondrial respiration (2-10x). Dose-addition isobole analysis showed synergy for the combination of 50% median effective dose (ED50) adriamycin with 50% ED50 Mce6/light in all assays (all P < or = .027). Antagonism was noted with the combination 25% ED50 adriamycin with 75% ED50 Mce6/light. Additivity and synergy were the predominant interactions for 75% ED50 adriamycin with 25% ED50 Mce6/light by dose-addition isobole analyses. Effect-addition isoboles showed a predominance of synergy, particularly for the combination 50% ED50 adriamycin with 50% ED50 Mce6/light.


CONCLUSIONS
Synergy and additivity are the primary in vitro interactions for the combination of adriamycin and Mce6/light in the dosage range tested. Reproductive capacity is more sensitive to these agents than is mitochondrial respiration.
Peterson
C M
CM
Department of Obstetrics and Gynecology, University of Utah, Salt Lake City 84132, USA.
Lu
J M
JM
Gu
Z W
ZW
Shiah
J G
JG
Lythgoe
K
K
Peterson
C A
CA
Straight
R C
RC
Kopecek
J
J
D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000633:toxicity*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007700:Kinetics; D008027:Light; D008652:Mesoporphyrins / Q000633:toxicity*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010051:Ovarian Neoplasms; D010101:Oxygen Consumption / Q000187:drug effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000633:toxicity*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C088297:meso-chlorin e(6) monoethylene diamine; D004317:Doxorubicin; D013936:Thymidine