Vincristine-resistant human cancer KB cell line and increased expression of multidrug-resistance gene.
A multidrug-resistant clone of human cancer KB cells was isolated by stepwise selection on exposure to increasing doses of vincristine. The final clone, VJ-300, obtained after ethylmethane sulfonate mutagenesis showed 400-fold higher resistance to vincristine than did KB cells. Cellular accumulation of vincristine in VJ-300 was decreased to less than one-tenth of that in KB. The cells were also cross-resistant to daunomycin, adriamycin, actinomycin D, colchicine and VP-16. During continuous culturing in the absence of any drug for several months, a different colchicine-resistant and multidrug-resistant clone, KB-C1, reverted almost completely to drug sensitivity, whereas drug resistance in VJ-300 was stably maintained. Amplification of the multidrug-resistance-1 (mdr-1) gene was more than 20-fold in KB-C1, but less than 2-fold in VJ-300. mdr-1 mRNA was, however, expressed in VJ-300 at a rate comparable to KB-C1. Acquisition of high multidrug resistance in VJ-300 might be correlated with both activated transcription of mdr-1 gene and amplification.
Kohno
K
K
Department of Biochemistry, Oita Medical School.
Kikuchi
J
J
Sato
S
S
Takano
H
H
Saburi
Y
Y
Asoh
K
K
Kuwano
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000345:Affinity Labels; D004351:Drug Resistance / Q000235:genetics*; D005784:Gene Amplification; D006801:Humans; D007624:KB Cells / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic; D014750:Vincristine / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000345:Affinity Labels; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014750:Vincristine