Activation of AMP-activated protein kinase sensitizes lung cancer cells


Objectives The therapeutic scheme for non-small cell lung cancer (NSCLC) patients can be improved if adapted to the individual response. For example, 60-70% of adenocarcinoma patients show response to EGFR-tyrosine kinase inhibitors in the presence of mutated EGFR. We searched for additional target molecules involved in the action of the EGFR-tyrosine kinase inhibitor erlotinib in the absence of EGFR mutations, which might be suitable for combinatorial therapy approaches. Materials and Methods Erlotinib-response associated proteins were investigated in patient-derived NSCLC mouse xenografts by reverse-phase protein array technology (RPPA) and Western blotting. A combinatorial treatment approach was carried out in NSCLC cell lines and H1299 mouse xenografts, and subsequently analysed for consequences in cell growth and signal transduction. Results AMP-activated protein kinase (AMPK) expression was increased in erlotinib responders before and after treatment. In a combinatorial approach, activation of AMPK by A-769662 and erlotinib treatment showed a synergistic effect in cell growth reduction and apoptosis activation in H1299 cells compared to the single drugs.

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@inproceedings{Hlsmann2014ActivationOA, title={Activation of AMP-activated protein kinase sensitizes lung cancer cells}, author={Helen J. H{\"{u}lsmann and Jana Rolff and Christian Bender and Mostafa Jarahian and Ulrike Korf and Ralf Herwig and Holger Fr{\"{o}hlich and Michael Thomas and Johannes Merk and Iduna Fichtner and Holger S{\"{u}ltmann and Ruprecht Kuner}, year={2014} }