title: In vivo acquired drug resistance and multidrug resistance gene (MDR1) expression in the KB carcinoma cell line xenotransplanted in nude mice.
abstract: We studied the correlation between in vivo responsiveness of KB xenografts to anticancer drugs and the expression level of the human multidrug resistance gene (MDR1) encoding P-Glycoprotein (P-Gp). We established KB xenografts (xeKB3-1 and xeKB8-5) by inoculating these in vitro lines into nude mice. The responsiveness was evaluated by an in vivo chemosensitivity assay (T/C; sensitive, < 50%). Xenograft xeKB3-1 was sensitive to vincristine (VCR) (T/C, 48%), and xeKB8-5 was resistant to VCR (T/C, 72%). We selected a VCR-resistant variant (xeKB3-1-R, T/C, 76%) by treating xeKB3-1 with VCR (1.2 mg/kg, x3) in vivo. The MDR1 expression was evaluated by a semi-quantitative assay using reverse transcription-polymerase chain reaction. A MDR1 expression pattern in xeKB3-1 and xeKB8-5 in vivo was the same as that to KB3-1 and KB8-5 in vitro. The xenograft xeKB3-1-R expressed definitive but significantly lower levels of MDR1 than xeKB8-5. These results suggest that acquired drug resistance is related to minimally enhanced expression of the P-Gp protein/MDR1 gene in KB xenografts in vivo.
authors.affiliation: Department of Pathology, Tokai University School of Medicine, Kanagawa Academy of Science and Technology, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Abe
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: R
authors.initials: R
authors.lastname: Saegusa
authors.forename: Y
authors.initials: Y
authors.lastname: Ueyama
authors.forename: T
authors.initials: T
authors.lastname: Ogata
authors.forename: N
authors.initials: N
authors.lastname: Tamaoki
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D017690:Cell Transplantation; D018076:DNA, Complementary; D018432:Drug Resistance, Multiple / Q000235:genetics*; D018014:Gene Transfer Techniques; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018076:DNA, Complementary