In vivo acquired drug resistance and multidrug resistance gene (MDR1) expression in the KB carcinoma cell line xenotransplanted in nude mice.
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.
Abe
Y
Y
Department of Pathology, Tokai University School of Medicine, Kanagawa Academy of Science and Technology, Japan.
Nakamura
M
M
Saegusa
R
R
Ueyama
Y
Y
Ogata
T
T
Tamaoki
N
N
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
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018076:DNA, Complementary