Antitumor activity of doxorubicin in combination with docetaxel against human breast cancer xenografts.
In this study we assessed the in vivo antitumor activity of combined docetaxel (DOCE) and doxorubicin (DXR) treatment using 2 human breast carcinoma cell xenografts (R-27 and MX-1) in the nude mouse model. The transplanted tumors were allowed to reach exponential growth, whereupon 10 or 40 mg DOCE per kg alone (i.p.), 8 mg DXR per kg alone (i.v.), or 10 mg/kg DOCE (i.p.) and 8 mg/kg of DXR (i.v.), in the sequence of DOCE followed by DXR, were administered. The in vivo antitumor activity of combined DOCE and DXR was synergistic against R-27 and additive against MX-1. P-glycoprotein (P-gp) was detected immunohistochemically, and was highly expressed in R-27, but not in MX-1. In conclusion, DOCE may increase the antitumor activity of DXR against P-gp-positive breast cancer xenografts, such that the DOCE and DXR combination may be a useful treatment in clinical breast cancer.
Egawa
Tomohisa
T
Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Kubota
Tetsuro
T
Suto
Akihiko
A
Otani
Yoshihide
Y
Furukawa
Toshiharu
T
Saikawa
Yoshiro
Y
Watanabe
Masahiko
M
Kumai
Koichiro
K
Kitajima
Masaki
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology*; D043823:Taxoids; D023041:Xenograft Model Antitumor Assays
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D017239:Paclitaxel