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.
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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.
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Gebregiworgis, T., Bhinderwala, F., Purohit, V. et al. Insights into gemcitabine resistance and the potential for therapeutic monitoring. Metabolomics 14, 156 (2018). https://doi.org/10.1007/s11306-018-1452-7
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DOI: https://doi.org/10.1007/s11306-018-1452-7