Literature DB >> 2906349

Vincristine-resistant human cancer KB cell line and increased expression of multidrug-resistance gene.

K Kohno1, J Kikuchi, S Sato, H Takano, Y Saburi, K Asoh, M Kuwano.   

Abstract

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.

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Year:  1988        PMID: 2906349      PMCID: PMC5917651          DOI: 10.1111/j.1349-7006.1988.tb01550.x

Source DB:  PubMed          Journal:  Jpn J Cancer Res        ISSN: 0910-5050


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