Decreased lactate concentration and glycolytic enzyme expression reflect inhibition of mTOR signal transduction pathway in B-cell lymphoma.

Research output: Contribution to journalJournal articleResearchpeer-review

  • Seung-Cheol Lee
  • Marzec, Michal Tomasz
  • Xiaobin Liu
  • Suzanne Wehrli
  • Kanchan Kantekure
  • Puthiyaveettil N. Ragunath
  • David S. Nelson
  • Edward J. Delikatny
  • Jerry D. Glickson
  • Mariusz A. Wasik
The application of kinase inhibitors in cancer treatment is growing rapidly. However, methods for monitoring the effectiveness of the inhibitors are still poorly developed and currently rely mainly on the tracking of changes in the tumor vol., a rather late and relatively insensitive marker of the therapeutic response. In contrast, MRS can detect changes in cell metab. and has the potential to provide early and patient-specific markers of drug activity. Using human B-cell lymphoma models and MRS, we have demonstrated that the inhibition of the mTOR signaling pathway can be detected in malignant cells in vitro and noninvasively in vivo by the measurement of lactate levels. An mTOR inhibitor, rapamycin, suppressed lactic acid prodn. in lymphoma cell line cultures and also diminished steady-state lactate levels in xenotransplants. The inhibition was time dependent and was first detectable 8 h after drug administration in cell cultures. In xenotransplants, 2 days of rapamycin treatment produced significant changes in lactic acid concn. in the tumor measured in vivo, which were followed by tumor growth arrest and tumor vol. regression. The rapamycin-induced changes in lactate prodn. were strongly correlated with the inhibition of expression of hexokinase II, the key enzyme in the glycolytic pathway. These studies suggest that MRS or 18F-fluorodeoxyglucose positron emission tomog. (FDG PET) detection of changes in glucose metab. may represent effective noninvasive methods for the monitoring of mTOR targeting therapy in lymphomas and other malignancies. Furthermore, the measurement of glucose metabolic inhibition by MRS or FDG PET imaging may also prove to be effective in monitoring the efficacy of other kinase inhibitors given that the rapamycin-sensitive mTOR lies downstream of many oncogenic signaling pathways. [on SciFinder(R)]
Original languageEnglish
JournalNMR in Biomedicine
Issue number1
Pages (from-to)106-114
Number of pages9
Publication statusPublished - 2013
Externally publishedYes

Bibliographical note

M1 - Copyright (C) 2018 American Chemical Society (ACS). All Rights Reserved.

CAPLUS AN 2013:7311(Journal; Online Computer File)

    Research areas

  • rapamycin anticancer mTOR inhibitor lactate glycolysis B cell lymphoma

ID: 202374751