Combined inhibition of ACK1 and AKT shows potential toward targeted therapy against KRAS-mutant non-small-cell lung cancer.

Combined inhibition of ACK1 and AKT shows potential toward targeted therapy against KRAS-mutant non-small-cell lung cancer. Bosn J Basic Med Sci. 2020 Jun 01;: Authors: Yu X, Liu J, Qiu H, Hao H, Zhu J, Peng S Abstract Non-small-cell lung cancer (NSCLC) with KRAS (Kirsten RAt Sarcoma 2 viral oncogene homolog) mutation has become a clinical challenge in cancer treatment as KRAS-mutant tumors are often resistant to conventional anti-tumor therapies. Activated CDC42-associated kinase 1 (ACK1), an activator of protein kinase B (AKT), is a promising target for KRAS-mutant tumor therapy, but the downstream ACK1 signaling remains poorly understood. The aim of this study was to evaluate the effectiveness of combined ACK1/AKT inhibition on the proliferation, migration, invasion, and apoptosis of KRAS-mutant NSCLC cell lines (NCI-H23, NCI-H358, and A549). The cells were treated with an inhibitor of either ACK1 (dasatinib or sunitinib) or AKT (MK-2206 or GDC-0068), and the optimal concentrations of the two yielding synergistic tumor-killing effects were determined by applying the Chou-Talalay equation for drug combinations. We showed that combined administration of ACK1 and AKT inhibitors at the optimal concentrations effectively suppressed NSCLC cell viability and promoted apoptosis, while inducing cell cycle arrest at the G2 phase. Moreover, NSCLC cell migration and invasion were inhibited by combined ACK1/AKT inhibition. These phenomena were...
Source: Bosnian Journal of Basic Medical Sciences - Category: General Medicine Tags: Bosn J Basic Med Sci Source Type: research