Metabolic state determines drug response in liver cancer

Drug resistance is one of the most challenging problems in liver cancer research. The hepatocellular carcinoma cell line HLE is highly dependent on exogenous glutamine for proliferation. In this cell line, we have found that glutamine deprivation leads to proliferation arrest, phosphorylation of extracellular signal-regulated kinase (ERK), and metabolic alterations at gene, protein, metabolite levels. Interestingly, while HLE cells respond to kinase inhibitors in their unperturbed metabolic state, they display pro-tumourigenic phenotypes such as increased aerobic glycolysis and proliferation when treated with inhibitors of MAPK/ERK pathway in the impaired metabolic state induced by glutamine deprivation. Thus, the aim of this microarray analysis is to determine the genomic alterations that accompany glutamine deprivation and treatment with pERK inhibitor U0126. The anticipated alterations could shed light on novel molecular mechanisms underlying drug resistance, and may be useful for predicting therapeutic response in liver cancer. This microarray data includes the following conditions (and replicates): HLE cells cultured in complete media (n=2), HLE cells cultured in glutamine-free media (n=2), and HLE cells cultured in glutamine-free media containing 20 µM U0126 (n=2).