In vitro characterisation of soft tissue tumor chemosensitivity.
BACKGROUND
The benefit of performing chemotherapy on soft tissue sarcomas remains controversial. The present study deals with the in vitro characterisation of the influence of 3 antitumoral agents on the growth of 8 sarcoma cell lines.


METHODS
Cell growth was monitored by means of the MTT colorimetric assay, which was further validated by a direct cell counting method. The three drugs tested included doxorubicin (ADR), cisplatin (DDP) and dacarbazine (DTIC). ADR was tested at 10(-5) M, 10(-6) M and 10(-7) M; DDP at 10(-5) M, 10(-6) M and 10(-7) M; and DTIC at 10(-3) M, 10(-4) M and 10(-5) M. A combination of the three drugs was also tested in order to ascertain whether a synergistic effect on cell growth inhibition could be obtained. A potential antineoplastic agent-induced influence on cell growth was determined 3 days after the addition of the diverse drug(s) to the culture media. The cell concentration was specifically adapted to each cell line. The 8 cell lines included 3 leiomyosarcomas, 1 malignant mixed Müllerian tumour, 3 rhabdomyosarcomas and 1 fibrosarcoma.


RESULTS
The results show that of the three drugs tested, ADR was the most efficient in terms of the level of cell growth inhibition obtained and the number of cell lines whose growth was significantly inhibited. Of the three drugs, the least active was DDP. A significant synergistic effect was observed when the three drugs were added together to the culture medium. This synergistic effect was evident at the lowest doses tested for each drug. Whatever the histopathological type, the 8 cell lines exhibited a wide range of response to chemotherapy.


CONCLUSIONS
The present study shows that the inhibition induced by 10(-7) M ADR, 10(-7) M DDP and 10(-5) M DTIC on sarcoma cell line growth is significantly more efficient than if each agent is tested individually. The in vitro methodology used here fits in with clinical reality because it enables sarcoma cell heterogeneity to be taken into account.
Remmelink
M
M
Laboratory of Histology, Faculty of Medecine, Free University of Brussels, Belgium.
Salmon
I
I
Delville
J P
JP
Goldschmidt
D
D
Capel
P
P
Gebhart
M
M
Pasteels
J L
JL
Kiss
R
R
Darro
F
F
D000970:Antineoplastic Agents / Q000633:toxicity*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D003124:Colorimetry; D003606:Dacarbazine / Q000633:toxicity*; D004317:Doxorubicin / Q000633:toxicity*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007700:Kinetics; D011803:Quinine / Q000494:pharmacology; D015203:Reproducibility of Results; D012509:Sarcoma / Q000473:pathology*; D012983:Soft Tissue Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms; D014700:Verapamil / Q000494:pharmacology
D000970:Antineoplastic Agents; D003606:Dacarbazine; D004317:Doxorubicin; D011803:Quinine; D014700:Verapamil; D002945:Cisplatin