We wish to understand differences in metabolism and regulation between normal and cancer cells, and between cancer cells that are responsive to chemotherapy and those which exhibit pleiotropic drug resistance (PDR). Nuclear magnetic resonance (NMR) spectroscopy is used to monitor metabolic processes noninvasively, using a perfusion technique that we have developed in which cells are embedded in agarose gel threads. With this technique we have observed significant differences in the levels of major phosphate metabolites in wild type (WT) MCF-7 breast cancer cells, and an adriamycin resistant cell line (AdrR) that exhibits PDR. One of the major differences between normal and cancer cells is the control of energy metabolism. To follow glycolysis in WT and AdrR cells we improved the perfusion technique to enable us to use small volumes with 13C-glucose. We are able to monitor the rate of glucose uptake and the concomitant rate of lactate production with 13C NMR. The effects of inhibitors and effectors of individual enzymatic steps in glycolysis, such as phosphofructokinase (PFK) can then be compared in different cancer cell lines. As well as the breast cancer cell lines we are also carrying out parallel studies with small cell lung cancer cell lines. In order to extend these observations to noninvasive metabolic measurements in vivo we have designed and constructed a versatile NMR probe for our spectrometer. This contains the coils for irradiation and signals reception, and has a cradle to hold the animal. All components are adjustable and removeable, but currently are arranged to observe spectra from a subcutaneous tumor in a rodent. Eventually we anticipate extending these studies to larger animals, and hopefully to clinical trials of 31p MRS of breast cancer in humans.
