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Relationship between multidrug resistant gene expression and multidrug resistant-reversing effect of MS-209 in various tumor cells

  • Original Article
  • MS-209, Multidrug Resistance, RT-PCF
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Abstract

MS-209 is a novel quinoline compound which can overcome multidrug resistance (MDR) both in vitro and in vivo, while having a low level of side effects, and is now being evaluated in a clinical phase II study. Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantitative the expression levels ofMDR genes in various mouse and human tumor cell lines. TheMDR gene and the βactin gene, as the internal reference standard, were coamplified separately, and the relative expression of theMDR gene was represented by the MDR/β actin ratio. The in vitro MDR-reversing effect of MS-209 was then compared with theMDR gene expression (MDR/β actin ratio). We found a significant correlation between these two parameters. Moreover, a significant correlation was also observed between the level of expression of theMDR1 gene and that of P-glycoprotein in human cell lines. Therefore, the efficacy of MS-209 seems to specifically depend on the level ofMDR gene expression (P-glycoprotein). From these observations, it is suggested that RT-PCR assays ofMDR1 gene in tumor biopsy specimens might be an effective means to predict the response of tumor cells to combination therapy with MS-209.

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Abbreviations

MDR :

multidrug resistance

ADM :

adriamycin

VCR :

vincristine

MTT :

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

RT :

reverse transcription

PCR :

polymerase chain reaction,SDS sodium dodecyl sulfate

PMSF :

phenylmethylsulfonyl fluoride

EtBr :

ethidium bromide

IC 50 :

concentration producing 50% inhibition

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Authors and Affiliations

  1. Institute of Biological Science, Mitsui Pharmaceuticals, Inc., 297, Mobara, Chiba, Japan

    Makoto Baba, Osamu Nakanishi, Wakao Sato, Akiko Saito, Yukio Miyama, Osamu Yano & Shizuo Shimada

  2. Life Science Laboratory, Mitsui Toatsu Chemicals, Inc., 297, Mobara, Chiba, Japan

    Nobuyuki Firkazawa

  3. Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, 113, Bunkyo-ku, Tokyo, Japan

    Mikihiko Naito & Takashi Tsuruo

  4. Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Kami-ikebukuro, Toshima-ku, 170, Tokyo, Japan

    Takashi Tsuruo

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  1. Makoto Baba
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  2. Osamu Nakanishi
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  9. Mikihiko Naito
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Baba, M., Nakanishi, O., Sato, W. et al. Relationship between multidrug resistant gene expression and multidrug resistant-reversing effect of MS-209 in various tumor cells. Cancer Chemother. Pharmacol. 36, 361–367 (1995). https://doi.org/10.1007/BF00686183

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  • DOI: https://doi.org/10.1007/BF00686183

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