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Metabolomics

, 14:156 | Cite as

Insights into gemcitabine resistance and the potential for therapeutic monitoring

  • Teklab Gebregiworgis
  • Fatema Bhinderwala
  • Vinee Purohit
  • Nina V. Chaika
  • Pankaj K. Singh
  • Robert Powers
Short Communication
  • 172 Downloads

Abstract

Introduction

Gemcitabine is an important component of pancreatic cancer clinical management. Unfortunately, acquired gemcitabine resistance is widespread and there are limitations to predicting and monitoring therapeutic outcomes.

Objective

To investigate the potential of metabolomics to differentiate pancreatic cancer cells that develops resistance or respond to gemcitabine treatment.

Results

We applied 1D 1H and 2D 1H–13C HSQC NMR methods to profile the metabolic signature of pancreatic cancer cells. 13C6-glucose labeling identified 30 key metabolites uniquely altered between wild-type and gemcitabine-resistant cells upon gemcitabine treatment. Gemcitabine resistance was observed to reprogram glucose metabolism and to enhance the pyrimidine synthesis pathway. Myo-inositol, taurine, glycerophosphocholine and creatinine phosphate exhibited a “binary switch” in response to gemcitabine treatment and acquired resistance.

Conclusion

Metabolic differences between naïve and resistant pancreatic cancer cells and, accordingly, their unique responses to gemcitabine treatment were revealed, which may be useful in the clinical setting for monitoring a patient’s therapeutic response.

Keywords

NMR metabolomics Pancreatic cancer Gemcitabine Drug resistance 

Notes

Acknowledgements

This work was supported in part by funding from the National Institutes of Health Grant No. (R01 CA163649, NCI) to P.K.S. and R.P.; the Redox Biology Center (Grant No. P30 GM103335, NIGMS) to R.P.; the Nebraska Center for Integrated Biomolecular Communication (Grant No. P20 GM113126, NIGMS) to R.P.; American Association for Cancer Research (AACR)-Pancreatic Cancer Action Network (PanCAN) Career Development Award (Grant No. 30-20-25-SING) to P.K.S.; the Specialized Programs for Research Excellence (Grant No. SPORE, 2P50 CA127297, NCI) to P.K.S.; Pancreatic Tumor Microenvironment Research Network (Grant No. U54, CA163120, NCI) to P.K.S.; and Fred & Pamela Buffett Cancer Center Support Grant (Grant No. P30CA036727) to P.K.S. and R.P. The research was performed in facilities renovated with support from the National Institutes of Health (Grant No. RR015468-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors have no conflict of interest to declare.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

11306_2018_1452_MOESM1_ESM.pdf (586 kb)
Supplementary material 1 (PDF 585 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of Nebraska-LincolnLincolnUSA
  2. 2.Nebraska Center for Integrated Biomolecular CommunicationUniversity of Nebraska-LincolnLincolnUSA
  3. 3.The Eppley Institute for Research in Cancer and Allied DiseasesUniversity of Nebraska Medical CenterOmahaUSA
  4. 4.Department of Biochemistry and Molecular BiologyUniversity of Nebraska Medical CenterOmahaUSA
  5. 5.Department of Pathology and MicrobiologyUniversity of Nebraska Medical CenterOmahaUSA
  6. 6.Department of Genetics, Cell Biology and AnatomyUniversity of Nebraska Medical CenterOmahaUSA

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