title: [Combined effects of toremifene and paclitaxel on human breast cancer cell lines].
abstract: Effects of toremifene (TOR) in combination with paclitaxel (TXL) on various human breast cancer cell lines were evaluated. TOR and TXL exhibited additive effects on estrogen receptor (ER)-positive cancer cell lines, MCF-7 and T-47D, and a sub-additive effect on a tamoxifen (TAM)-resistant line, T-47D/TAM. To all three ER-negative cancer cell lines, the combined treatment also showed additive effects on MDA-MB-134VI, MDA-MB-231 and MDA-MB-453. Furthermore, a synergistic effect was observed on a multi-drug resistant (MDR) line, Adr. This synergistic effect was more potent in the combination with TOR than that with TAM. The combined treatment increased intracellular TXL, and the accumulation by TOR was 1.5-fold that by TAM. Consequently, the ratio of G2M arrested cells was higher, with statistical significance, in the TOR combination than in the TAM combination. In addition, these synergistic effects in MDR cells were also observed in the combination of TXL with major clinical active metabolites, N-desmethyl-TOR (TOR-1) and 4-hydroxy-TOR (TOR-2). These results suggest that the combination therapy of TOR and TXL might be an effective clinical treatment for breast cancer patients.
authors.affiliation: Research and Development Division, Nippon Kayaku Co., Ltd.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Maruyama
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kuroiwa
authors.forename: Atsuya
authors.initials: A
authors.lastname: Saimoto
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Nishikawa
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D004357:Drug Synergism; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D017312:Toremifene / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D020845:Selective Estrogen Receptor Modulators; D017312:Toremifene; D017239:Paclitaxel