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1H HR-MAS NMR Based Metabolic Profiling of Lung Cancer Cells with Induced and De-Induced Cisplatin Resistance to Reveal Metabolic Resistance Adaptations
Authors:Martina Vermathen  Hendrik von Tengg-Kobligk  Martin Nils Hungerbühler  Peter Vermathen  Nico Ruprecht
Institution:1.Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, 3012 Bern, Switzerland;2.Department of Diagnostic, Interventional and Pediatric Radiology, Bern University Hospital, University of Bern, 3010 Bern, Switzerland; (H.v.T.-K.); (M.N.H.);3.Department of BioMedical Research, University of Bern, 3008 Bern, Switzerland;4.University Institute of Diagnostic and Interventional Neuroradiology, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
Abstract:Cisplatin (cisPt) is an important drug that is used against various cancers, including advanced lung cancer. However, drug resistance is still a major ongoing problem and its investigation is of paramount interest. Here, a high-resolution magic angle spinning (HR-MAS) NMR study is presented deciphering the metabolic profile of non-small cell lung cancer (NSCLC) cells and metabolic adaptations at different levels of induced cisPt-resistance, as well as in their de-induced counterparts (cells cultivated in absence of cisPt). In total, fifty-three metabolites were identified and quantified in the 1H-HR-MAS NMR cell spectra. Metabolic adaptations to cisPt-resistance were detected, which correlated with the degree of resistance. Importantly, de-induced cell lines demonstrated similar metabolic adaptations as the corresponding cisPt-resistant cell lines. Metabolites predominantly changed in cisPt resistant cells and their de-induced counterparts include glutathione and taurine. Characteristic metabolic patterns for cisPt resistance may become relevant as biomarkers in cancer medicine.
Keywords:cisplatin  cisPt resistance  non-small cell lung cancer  NSCLC  HR-MAS NMR  metabolomics
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