We highlight the conventional mechanisms of drug resistance elicited by the complex heterogeneous microenvironment of NSCLC during targeted therapy, including mutations in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), the receptor tyrosine kinase ROS proto-oncogene 1 (ROS1), and the serine/threonine-protein kinase BRAF (v-Raf murine sarcoma viral oncogene homolog B).
We further showed that downregulation of AKT signaling activity by using AKT inhibitor LY294002 markedly inhibited NSCLC cell proliferation and resistance to doxorubicin induced by VASH2.
In conclusion, the results of the present study identified miR‑497 as a potential tumor suppressor gene in NSCLC that may function via repressing FGFR1 expression, and AKT and JNK signaling.
Rescue experiment demonstrated that inhibition of either AKT or Snail could partially counteract the promoting effect of FAM83A overexpression in NSCLC metastasis.
Our findings showed important roles of phosphorylation activation of AKT and ERK and potential interplay and cooperation between NF-κB and HIF-1α in PD-L1 expression regulation by EGFR mutants in NSCLC.
Collectively, our results, both <i>in vivo</i> and <i>in vitro</i>, demonstrate that BBD leads to autophagic cell death through downregulating the PI3K/AKT/mTOR signaling pathway and improved the antitumor effects of cisplatin in non-small cell lung cancer (NSCLC).
Both maintained T-cell responses in peripheral blood to oncogenic driver mutations - BRAF-N581I in the NSCLC and AKT1-E17K in the CRC - years after treatment initiation.
Mechanistically, we found that circFGFR3 promoted NSCLC cell invasion and proliferation via competitively combining with miR-22-3p to facilitate the galectin-1 (Gal-1), p-AKT, and p-ERK1/2 expressions.
In conclusion, quinalizarin may partially sensitize cells to icotinib by inhibiting proliferation and promoting apoptosis mediated by AKT and ERK in EGFR‑TKI resistant NSCLC cell lines.
Our results suggest that miR-503 inhibits NSCLC progression by targeting PDK1/PI3K/AKT pathway, potentiating the use of miR-503 as a biomarker and therapeutic target for NSCLC.
The present findings suggested that treatment with pemetrexed may exhibit synergistic effects with PTEN on lung cancer cells via the inhibition of the PI3K/AKT/mTOR signaling pathway and through carbohydrate metabolism, and treatment with pemetrexed combined with PTEN overexpression may represent a novel therapeutic strategy for the treatment of NSCLC.
In addition, eEF1A2 and STAT1 siRNA transfections suggested that both STAT1 and eEF1A2 prevent AKT phosphorylation known for enhancing gefitinib resistance in NSCLC.
We have conducted this study to check the effect of VCN-2 on the cell viability and the effect on PTEN (Phosphatase and tensin homolog), PI3KCA (Phosphatidylinositol 4, 5-biphosphate 3-kinase catalytic subunit alpha isoform/PI3K 110α subunit), and Akt1 when VCN-2 was used alone and in combination with radiation in the NSCLC cell line NCI-H23 (H23).