The effects of Akt1/Akt2 selective inhibition on tumorigenic properties of NSCLC cells

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Briah, Ritesh
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University of Guelph

Akt is a key signaling kinase that is hyper-activated in many non-small cell lung cancer (NSCLC) cases and is involved in cell survival, proliferation, migration and metabolism. Recent research has shown that the three isoforms of Akt have non-redundant roles in cell signaling and thus this study aims to compare the effects of Akt1 (A-674563), Akt2 (CCT128930), and pan-Akt (MK-2206) inhibition on tumorigenic properties of A549 and NCI-H358 cells. Cell survival curves demonstrated that all inhibitors effectively reduce cell viability, however Akt1 inhibition was the most effective. Additionally, Akt1 inhibition was found to be more effective in reducing cell migration and inducing apoptosis. Interestingly, cell cycle analysis of Akt1 inhibition also indicated a possible G2/M phase block. Taken together, these results suggest that Akt1 inhibition is a more effective therapeutic strategy for human NSCLC cells than either Akt2 inhibition or inhibition of all 3 Akt isoforms.

lung cancer, NSCLC, molecular targets, inhibitors