Evaluation of cell proliferation and cell death based assays in chemosensitivity testing.
BACKGROUND
Drug sensitivity testing (DST) is used to predict the clinical response to chemotherapy with limited success. Our objective was to evaluate assays that measure cell proliferation or apoptosis in determining sensitivity of ovarian cancer cells to cisplatin and paclitaxel.


METHODS
Four ovarian cancer lines were used. LD10-LD90 doses were determined by viability assays. Assays measuring cell proliferation, sulforhodamine-B (SRB), tritiated thymidine; and cell death, diphenylamine or DNA histone ELISA were compared.


RESULTS
SRB assay was consistent and sensitive. Histone ELISA correlated with the viability assay at high doses. The [3H] thymidine test was not sensitive and resulted in false positive responses. While less sensitive, detection of apoptosis by diphenylamine assay shows a similar trend to histone ELISA.


CONCLUSIONS
We demonstrate significant differences between the various assays. Most of these assays are better predictors of resistance. Further studies are needed to determine the best correlation between in vitro testing and responses in vivo.
Gerçel-Taylor
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Department of Obstetrics and Gynecology, University of Louisville School of Medicine, KY 40202, USA. catayl01@gwise.louisville.edu
Ackermann
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MA
Taylor
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DD
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004159:Diphenylamine / Q000032:analysis; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005456:Fluorescent Dyes; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D012235:Rhodamines; D013936:Thymidine / Q000032:analysis / Q000378:metabolism
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D005456:Fluorescent Dyes; D012235:Rhodamines; C022027:lissamine rhodamine B; D004159:Diphenylamine; D017239:Paclitaxel; D002945:Cisplatin; D013936:Thymidine