期刊
MOLECULAR CANCER RESEARCH
卷 16, 期 3, 页码 453-460出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-17-0458
关键词
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资金
- NIH/NCI Cancer Center [P30 CA008748]
- NIH/NCI [R01 CA195476]
- NIH/NIBIB [R00 EB014328]
- Memorial Sloan Kettering's Center for Molecular Imaging and Nanotechnology (CMINT)
The PI3K/AKT/mTOR (PAM) signaling pathway is frequently mutated in prostate cancer. Specific AKT inhibitors are now in advanced clinical trials, and this study investigates the effect of MK2206, a non-ATP-competitive inhibitor, on the cellular metabolism of prostate cancer cells. We observed a reduction in cell motility and aerobic glycolysis in prostate cancer cells with treatment. These changes were not accompanied by a reduction in the ratio of high-energy phosphates or a change in total protein levels of enzymes and transporters involved in glycolysis. However, a decreased ratio of NAD(+)/NADH was observed, motivating the use of hyperpolarized magnetic resonance spectroscopy (HP-MRS) to detect treatment response. Spectroscopic experiments were performed on tumor spheroids, 3D structures that self-organize in the presence of an extracellular matrix. Treated spheroids showed decreased lactate production with on-target inhibition confirmed using IHC, demonstrating that HP-MRS can be used to probe treatment response in prostate cancer spheroids and can provide a biomarker for treatment response.
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