Advantage of in vivo chemosensitivity assay to detect vincristine-resistance in a human epidermoid carcinoma xenograft.
We examined both in vitro and in vivo chemosensitivity of the human epidermoid carcinoma xenograft xeKB3-1-R which shows overexpression of the multidrug resistance gene (MDR1). XeKB3-1-R was sensitive to vincristine (VCR, 6%) and doxorubicin (DOX, 9%) in the adhesive tumor cell culture system in vitro. However, this xenograft showed decreased sensitivity to VCR (65%) and DOX (42%) in an in vivo chemosensitivity assay. The in vivo resistance of xeKB3-1-R to both VCR and DOX was reversed by coadministration of cyclosporin A (VCR 22%, DOX 11%). The xenograft xeKB3-1-R expressed significantly higher levels of MDR1 than xeKB3-1. The results confirmed that multidrug resistance in xeKB3-1-R was related to enhanced MDR1 expression in vivo. The observed discrepancies between in vitro and in vivo chemosensitivities suggest that the in vivo sensitivity assay more accurately reflects drug resistance as a result of low-level MDR1 overexpression in solid tumors.
Abe
Y
Y
Department of Pathology, Tokai University School of Medicine, Kanagawa, Japan.
Yamazaki
H
H
Oshika
Y
Y
Suto
R
R
Tsugu
A
A
Ota
E
E
Satoh
H
H
Ohnishi
Y
Y
Yanagawa
T
T
Ueyama
Y
Y
Tamaoki
N
N
Nakamura
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy*; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014750:Vincristine; D004317:Doxorubicin