title: Antitumor activity of doxorubicin in combination with docetaxel against human breast cancer xenografts.
abstract: 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.
authors.affiliation: Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Egawa
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kubota
authors.forename: Akihiko
authors.initials: A
authors.lastname: Suto
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Otani
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Furukawa
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saikawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kumai
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitajima
mesh_terms: 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
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; D017239:Paclitaxel