Docetaxel enhances the cytotoxicity of anthracyclines by increasing intracellular drug accumulation.
We assessed the combined antitumor activity of docetaxel and doxorubicin (DXR) and tetrahydropyranyl-adriamycin (THP) using the human breast carcinoma cell lines R-27 and MDA-MB-231. Synergistic antitumor activity was observed for both combined docetaxel and DXR, and docetaxel and THP against R-27 cells when contacted simultaneously. However, only additive effects were observed against MDA-MB-231 cells. Intracellular concentrations of DXR and THP in R-27 cells were significantly increased by docetaxel pretreatment, however, this increase was not observed in MDA-MB-231 cells, which exhibited only additive sensitivity to the treatment. Thus, docetaxel increased the antitumor activity of anthracyclines by increasing their intracellular concentrations.
Egawa
Tomohisa
T
Department of Surgery, School of Medicine, Keio University, Tokyo 160-8582, Japan.
Kubota
Tetsuro
T
Suto
Akihiko
A
Otani
Yoshihide
Y
Furukawa
Toshiharu
T
Watanabe
Masahiko
M
Kumai
Koichiro
K
Kitajima
Masaki
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D043823:Taxoids; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; C027260:pirarubicin; D017239:Paclitaxel