In vitro efficacy of chemotherapeutics as determined by 50% inhibitory concentrations in cell cultures of mammary gland tumors obtained from dogs.
OBJECTIVE
To determine the 50% inhibitory concentration (IC-50) of carboplatin, cisplatin, and doxorubicin in cell cultures of mammary gland tumors obtained from dogs and to assess whether in vitro efficacy was within the range of clinically relevant concentrations,


METHODS
30 mammary gland tumors excised from dogs.


METHODS
Cell cultures were established from the 30 tumors. Cultures then were treated with carboplatin, cisplatin, or doxorubicin. Growth inhibition of cultures was assessed via DNA measurement 24, 48, and 72 hours after treatment. The IC-50 values were calculated by use of linear interpolation.


RESULTS
Cultures varied in their pattern of susceptibility. Doxorubicin induced significantly lower IC-50 values than the platinum derivatives. Cisplatin and carboplatin had comparable effects. The IC-50 values for carboplatin and doxorubicin were in the range of clinically relevant concentrations, but only part of the cisplatin cultures had IC-50 values within clinically relevant concentrations. We did not detect differences in the in vitro susceptibility among subtypes of tumors (ie, adenocarcinoma, solid carcinoma, malignant mixed tumor).


CONCLUSIONS
The IC-50 values determined in this study allowed assessment of in vitro drug efficacy of chemotherapeutics in cultures of mammary gland tumors obtained from dogs. Variations in susceptibility were evident and emphasize the importance of assessing susceptibility and resistance patterns for each tumor. Prospective studies to assess direct correlations between in vitro and in vivo efficacy must be performed to determine the clinical predictive value of this in vitro chemosensitivity assay for treatment of dogs with mammary gland tumors.
Simon
D
D
Small Animal Clinic, Hannover School of Veterinary Medicine, Germany.
Knebel
J W
JW
Baumgartner
W
W
Aufderheide
M
M
Meyer-Lindenberg
A
A
Nolte
I
I
D000230:Adenocarcinoma / Q000188:drug therapy / Q000662:veterinary*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000032:analysis / Q000096:biosynthesis; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D007150:Immunohistochemistry / Q000662:veterinary; D020128:Inhibitory Concentration 50; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy*; D018198:Mixed Tumor, Malignant / Q000188:drug therapy / Q000662:veterinary*; D018709:Statistics, Nonparametric; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004317:Doxorubicin; D016190:Carboplatin; D002945:Cisplatin