title: Tamoxifen circumvents the multidrug resistance in fresh human gastrointestinal cancer cells.
abstract: The resistance to doxorubicin (DOX) is mainly due to the effect of P-glycoprotein encoded by the multidrug resistance-1 (mdr1) gene. Tamoxifen (TAM) has been shown to circumvent multidrug resistance in P-glycoprotein-expressing cell lines. In the present study, we clarified the augmentation of DOX sensitivity by TAM using MTT assay in highly purified fresh human tumor cells obtained from 85 cancer patients. Moreover, the correlation between DOX sensitivity and P-glycoprotein expression was assessed by flow cytometry. DOX sensitivity was decreased in proportion to P-glycoprotein expression. The cytotoxicity of DOX was increased by TAM in tumor cells possessing low DOX sensitivity. Moreover, there was a significant correlation between the effect of TAM on cytotoxicity and P-glycoprotein expression. The concentration of DOX in tumor cells was increased in combined exposure of TAM with DOX, compared with the exposure of DOX alone. Thus, TAM might be able to circumvent DOX-resistance for treatment in cancer patients.
authors.affiliation: Second Department of Surgery, Wakayama Medical School, 27-Shichibancho, Wakayama, 640, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hotta
authors.forename: H
authors.initials: H
authors.lastname: Tanimura
authors.forename: H
authors.initials: H
authors.lastname: Yamaue
authors.forename: M
authors.initials: M
authors.lastname: Iwahashi
authors.forename: M
authors.initials: M
authors.lastname: Tani
authors.forename: T
authors.initials: T
authors.lastname: Tsunoda
authors.forename: M
authors.initials: M
authors.lastname: Tamai
authors.forename: K
authors.initials: K
authors.lastname: Noguchi
authors.forename: S
authors.initials: S
authors.lastname: Mizobata
authors.forename: K
authors.initials: K
authors.lastname: Arii
authors.forename: H
authors.initials: H
authors.lastname: Terasawa
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D013629:Tamoxifen; D004317:Doxorubicin