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

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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.