Collateral methotrexate resistance in cisplatin-selected murine leukemia cells

Brazilian Journal of Medical and Biological Research

A. Bhushan¹  M.p. Hacker²  T.r. Tritton² 

[1] ,Idaho State UniversityPocatello ID ,USA

关键词: methotrexate transport;    resistance;    cisplatin;    leukemia;    phosphorylation;   

DOI  :  10.1590/S0100-879X1999000700005

来源: SciELO

【 摘 要 】

Resistance to anticancer drugs is a major cause of failure of many therapeutic protocols. A variety of mechanisms have been proposed to explain this phenomenon. The exact mechanism depends upon the drug of interest as well as the tumor type treated. While studying a cell line selected for its resistance to cisplatin we noted that the cells expressed a >25,000-fold collateral resistance to methotrexate. Given the magnitude of this resistance we elected to investigate this intriguing collateral resistance. From a series of investigations we have identified an alteration in a membrane protein of the resistant cell as compared to the sensitive cells that could be the primary mechanism of resistance. Our studies reviewed here indicate decreased tyrosine phosphorylation of a protein (molecular mass = 66) in the resistant cells, which results in little or no transfer of methotrexate from the medium into the cell. Since this is a relatively novel function for tyrosine phosphorylation, this information may provide insight into possible pharmacological approaches to modify therapeutic regimens by analyzing the status of this protein in tumor samples for a better survival of the cancer patients.

【 授权许可】

CC BY   
 All the contents of this journal, except where otherwise noted, is licensed under a Creative Commons Attribution License