Open AccessVincristine‐resistant Human Cancer KB Cell Line and Increased Expression of Multidrug‐resistance Gene
Author(s) -
Kohno Kimitoshi,
Kikuchi Junko,
Sato Shinichi,
Takano Hiroshi,
Saburi Yoshio,
Asoh Kuniichi,
Kuwano Michihiko
Publication year - 1988
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1988.tb01550.x
Subject(s) - multiple drug resistance , vincristine , clone (java method) , biology , drug resistance , microbiology and biotechnology , colchicine , gene , cell culture , cancer research , chemotherapy , genetics , cyclophosphamide
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.