[Study on the relationship between the resistance to MTX and the transport protein superfamily of ATP-binding cassette that induces multiple drug resistance].
A major problem, especially the multidrug resistance, in chemotherapy was the resistance to the chemotherapeutic agents. ATP-binding cassette transporter superfamily that mediated the efflux of drugs was involved in multidrug resistance. In order to understand the relationship between the resistance to MTX and the transport protein superfamily of ATP-binding cassette, and to investigate the mechanism of resistance to MTX, the study detected the expressions of mdr1, mrp1, mrp2, mrp3, mrp5, mrp6 and abcg2 that encoded the transport proteins by SuperArray analysis and the expressions of MRP1and MRP5 proteins by Western blot analysis. The results showed that the multidrug resistance proteins were the chief member of ATP-binding cassette transporter superfamily related to resistance to MTX. And the high expression levels of mrp1 and mrp5 were detected. Moreover, it revealed by SuperArray analysis that expression of mrp5 in MTX-resistant cells was significantly higher than that in normal mouse cells. Besides, corresponding excessive expression of MRP5 protein in MTX-resistant cells was also confirmed by Western blot. So, MRP5 could play important roles in the resistance to MTX and would be a new potential drug target.
Zhang
Chun-Yu
CY
Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China. zhangcy@ems.hrbmu.edu.cn
Feng
Yuan-Xi
YX
Li
Pu
P
Fu
Song-Bin
SB
D016475:3T3 Cells; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005786:Gene Expression Regulation; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis
D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D008727:Methotrexate; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C492376:Abcc5 protein, mouse; C421109:multidrug resistance-associated protein 1