Targeting mammalian target of rapamycin to both downregulate and disable the P-glycoprotein pump in multidrug-resistant B-cell lymphoma cell lines

Iliodora Pop, Laurentiu Pop, Maria Ana Ghetie, Ellen S. Vitetta

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Previous studies have shown that rapamycin can inhibit the growth of several different types of human tumor cells in vitro. In certain cases, it can reverse the phenotype of multidrug resistant (MDR) cells. However, there is limited information concerning its effect on P-glycoprotein (P-gp), a pump that is responsible for chemoresistance in many MDR cells. We investigated the effect of rapamycin on both P-gp function and the MDR phenotype in four cell lines. One cell line was also xenografted into SCID mice to determine whether rapamycin would chemosensitize the cells in vivo. Because rapamycin targets the mammalian target of rapamycin (mTOR) pathway, we also used our cells to confirm that rapamycin modified the expression of mTOR and effectively suppressed the phosphorylation of two downstream effector molecules in the mTOR pathway, S6K1, and 4E-BP1. We demonstrated that it inhibited the growth of the three cell lines in vitro and one in vivo showing that it modulated both the expression and function of P-gp and chemosensitized the three cell lines as effectively as verapamil.

Original languageEnglish (US)
Pages (from-to)1155-1162
Number of pages8
JournalLeukemia and Lymphoma
Volume50
Issue number7
DOIs
StatePublished - Aug 17 2009

Keywords

  • MDR lymphoma
  • MTOR inhibitors
  • P-glycoprotein

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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