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AMPK is a cellular energy sensor that negatively regulates the mTOR signaling pathway. As mTOR plays critical roles in cell growth and tumorigenesis of renal cell carcinoma (RCC), we examined whether exogenous induction of AMPK activity exhibits inhibitory effects on growth and survival of renal cell carcinoma cells. Activation of AMPK by AICAR resulted in potent suppressive effects on RCC growth, while combinations of AICAR with statins were potent inducers of apoptosis in such cells. The effects of AICAR resulted from inhibition of mTOR and its effectors, resulting from induction of AMPK activity. Similar results on RCC cell growth were obtained when combinations of metformin with statins were examined. Importantly, studies to examine the effects of AICAR or metformin, alone or in combinations with statins, on anchorageindependent growth demonstrated potent suppressive effects on RCC tumorigenicity in vitro. Altogether, our studies demonstrate that AMPK plays critical regulatory roles in the regulation of growth of RCC cells and raise the prospect of future use of AMPK activators in the treatment of renal cell carcinoma in humans.

While survival periods for patients with localized prostate cancer have increased, there is still no curative therapy for metastatic disease. Using non-invasive bioluminescent imaging, we designed a comprehensive murine model to monitor tumor location and expansion. We detected micrometastases after one week that correlated by gross necropsy, autoradiography, and histopathology with organ and skeletal lesions seen clinically. We calculated in vivo kinetics for tumor growth based on biophoton emissions and observed significantly faster growth of bone lesions and of overall tumor burden in young mice compared to old mice. This model provides a controllable biological system for further investigation into the pathogenesis of metastatic prostate cancer and evaluation of new therapies.