Study summary · research use only
AMPK as a therapeutic target in renal cell carcinoma
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This in vitro study (human renal cell carcinoma cell lines) examined AMPK as a potential therapeutic target, testing whether inducing AMPK activity affects growth and survival of renal cell carcinoma (RCC) cells. Activation of AMPK using AICAR was reported to suppress RCC growth, and combining AICAR with statins was associated with increased apoptosis induction in these cells, attributed to inhibition of mTOR and its downstream effectors via AMPK activation. Similar results were reported for combinations of metformin with statins. The authors also reported suppressive effects on anchorage-independent RCC growth in vitro, and concluded AMPK plays a regulatory role in RCC cell growth, raising the prospect of future study of AMPK activators for renal cell carcinoma treatment in humans.
Abstract
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 anchorage-independent 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.
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