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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

A novel quinoline derivative, MS-209, overcomes drug resistance of human lung cancer cells expressing the multidrug resistance-associated protein ( MRP) gene.

PURPOSE AND METHODS: MS-209 is a newly synthesized quinoline compound used orally to overcome human P-glycoprotein (Pgp)-mediated multidrug resistance (MDR). The multidrug resistance-associated protein ( MRP) gene is thought to play an important role in MDR in lung cancer. To investigate whether MS-209 could also overcome MRP- mediated MDR, we examined the effect of the compound using a cytotoxicity assay on MDR1 gene-negative drug-selected MDR and wildtype lung cancer cells with various levels of MRP gene expression. The effects of MS-209 were compared with those of verapamil (VER) and cyclosporin A (CsA). The level of MRP gene expression in the cells was evaluated semiquantitatively by RT-PCR. For vincristine (VCR), intracellular accumulation of [3H]-VCR was measured with or without MS-209. RESULTS: In MDR UMCC-1/VP small-cell lung carcinoma cell line, 5 microM of MS-209 and VER enhanced the cytotoxicity of etoposide, doxorubicin (DOX) and VCR more than twofold, and completely reversed the resistance to VCR. The mean reversing effects of MS-209 on DOX and VCR were significantly stronger than those of VER and CsA. In wildtype non-small-cell lung carcinoma cells, the effects of MS-209 were almost equal to those of VER and CsA. The effect of these three agents correlated with the level of MRP gene expression. The MS-209-induced increase in intracellular accumulation of VCR was proportional to the level of MRP gene expression in these cells. CONCLUSION: Our results indicate that MS-209 is a potentially useful drug that can overcome MRP- mediated intrinsic and acquired MDR in human lung cancer.[1]

References

  1. A novel quinoline derivative, MS-209, overcomes drug resistance of human lung cancer cells expressing the multidrug resistance-associated protein (MRP) gene. Narasaki, F., Oka, M., Fukuda, M., Nakano, R., Ikeda, K., Takatani, H., Terashi, K., Soda, H., Yano, O., Nakamura, T., Doyle, L.A., Tsuruo, T., Kohno, S. Cancer Chemother. Pharmacol. (1997) [Pubmed]
 
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