RELATIONSHIP BETWEEN MULTIDRUG-RESISTANT GENE-EXPRESSION AND MULTIDRUG-RESISTANT REVERSING EFFECT OF MS-209 IN VARIOUS TUMOR-CELLS

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 quantitate the expression levels of MDR genes in various mouse and human tumor cell lines. The MDR gene and the B actin gene, as the internal reference standard, were coamplified separately, and the relative expression of the MDR gene was represented by the MDR/B actin ratio. The in vitro MDR-reversing effect of MS-209 was then compared with the MDR gene expression (MDR/B actin ratio). We found a significant correlation between these two parameters. Moreover, a significant correlation was also observed between the level of expression of the MDR1 gene and that of P-glycoprotein in human cell lines. Therefore, the efficacy of MS-209 seems to specifically depend on the level of MDR gene expression (P-glycoprotein). From these observations, it is suggested that RT-PCR assays of MDR1 gene in tumor biopsy specimens might be an effective means to predict the response of tumor cells to combination therapy with MS-209.