Biological properties of ten human ovarian carcinoma cell lines: calibration in vitro against four platinum complexes.
Ten human ovarian carcinoma cell lines have been studied as a potential in vitro screen for the development of novel anticancer platinum complexes. Lines have been established and developed both from solid and ascitic tumours, from pretreated and untreated patients, and are available at a range of in vitro passage numbers. The biological properties of the lines were consistent with them being human, epithelial and of ovarian carcinoma origin. Using a tritiated thymidine or leucine uptake method, and a 96 hour continuous drug exposure, the lines have been calibrated against four platinum-containing chemotherapeutic agents: cisplatin, iproplatin, carboplatin and tetraplatin. Striking differences in cytotoxicity were observed across the lines for each agent. Some lines were consistently resistant, others generally sensitive, whereas some showed clear evidence of differential sensitivity to a particular agent. Statistical analysis (Spearman rank correlation) involving the six possible pairings of drugs showed that cisplatin, iproplatin and carboplatin elicit a very similar pattern of response in these lines whereas tetraplatin elicits a completely different response pattern. Similar cytotoxicity values were obtained using a soft agar cloning assay. Results using a tetrazolium dye reduction assay, however, gave somewhat higher and more variable values, particularly with tetraplatin. The thymidine uptake assay will be adopted in further studies on a selected panel of six lines. This panel encompasses the spectra of sensitivities identified for each of the four agents against the original ten lines and may provide a useful screening facility for the development of novel platinum drugs, in that it detects both cell line-determined and structure-determined differences in cytotoxicity.
Hills
C A
CA
Drug Development Section, Institute of Cancer Research, Belmont, Sutton, Surrey, UK.
Kelland
L R
LR
Abel
G
G
Siracky
J
J
Wilson
A P
AP
Harrap
K R
KR
D000951:Antigens, Neoplasm / Q000032:analysis; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016190:Carboplatin; D002460:Cell Line; D002945:Cisplatin / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000276:immunology
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C023359:iproplatin; D016190:Carboplatin; D002945:Cisplatin; C049777:ormaplatin