Anti-neoplastic activity of topotecan versus cisplatin, etoposide and paclitaxel in four squamous cell cancer cell lines of the female genital tract using an ATP-Tumor Chemosensitivity Assay.
We evaluated the in vitro cytotoxicity of topotecan (TPT), versus cisplatin, etoposide (VP-16) and paclitaxel (PTX) in four squamous cell cancer cell lines of the cervix uteri and vulva. Four established human squamous cancer cell lines from the cervix uteri (A-431, Ca Ski and C-33) and vulva (CAL-39) were used. The cytotoxic effects of the agents were examined using the ATP-Tumor Chemosensitivity Assay (ATP-TCA). In addition to the single agents, the following combinations were tested: TPT+cisplatin, TPT+VP-16 and TPT+PTX. Three cell lines (C-33, Ca Ski and CAL-39) were highly sensitive to TPT, but one cell line (A-431) was less sensitive. Furthermore, the cytotoxic activity of TPT was superior to that of cisplatin in Ca Ski and C-33 cells, but inferior in CAL-39 and A-431. TPT was also more active than VP-16 in CAL-39 and Ca Ski. On the other hand, the cytotoxic activity of TPT was weaker than PTX in C-33, CAL-39 and A-431. TPT increased the cytotoxic activity of cisplatin and VP-16 in C-33, Ca Ski and A-431. However, synergistic features were observed only in A-431 cells. TPT also enhanced the cytotoxic activity of PTX in A-431 and Ca Ski. In CAL-39 and C-33, however, increased cytotoxic activity occurred only at higher drug concentrations, whereas antagonism was observed at lower drug concentrations. In conclusion, our results suggest that TPT has a significant cytotoxic effect on most squamous cell cancer cell lines which may be superior to cisplatin, VP-16 and PTX in some instances. Furthermore, TPT is likely to potentiate the cytotoxic activity of these agents in individual cell lines tested.
Boabang
P
P
Department of Gynecology and Obstetrics, University of Cologne Medical Center, Germany.
Kurbacher
C M
CM
Kohlhagen
H
H
Waida
A
A
Amo-Takyi
B K
BK
D000255:Adenosine Triphosphate / Q000032:analysis; D000970:Antineoplastic Agents / Q000633:toxicity*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000633:toxicity*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000633:toxicity; D005047:Etoposide / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006801:Humans; D008163:Luminescent Measurements; D017239:Paclitaxel / Q000008:administration & dosage / Q000633:toxicity; D019772:Topotecan / Q000008:administration & dosage / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*; D014846:Vulvar Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005047:Etoposide; D019772:Topotecan; D000255:Adenosine Triphosphate; D017239:Paclitaxel; D002945:Cisplatin