LY294002

Notably, LY294002 (a PI3K inhibitor) and Anisomycin (a JNK activator) partially reversed the anti-apoptotic and anti-inflammatory effects of PTE, respectively. This study provides the first integrated evidence combining network pharmacology and experimental validation that PTE protects against LIRI by modulating the PI3K/AKT and JNK/c-Jun signaling pathways, offering novel pharmacological insights into its translational potential in LIRI.

FGFR2 is lowly expressed in DFU and can exert a protective effect by activating the PI3K/Akt pathway. It is a candidate diagnostic biomarker and potential therapeutic target for DFU.

Mechanistically, APOE overexpression significantly activated the PI3K/AKT signaling pathway, and this effect was effectively reversed by the PI3K inhibitor LY294002. Consistently, APOE overexpression enhanced tumor growth in vivo. These findings indicate that APOE promotes glioma progression through nuclear activity and activation of the PI3K/AKT signaling pathway, highlighting APOE-related signaling as a potential therapeutic target in glioma.

Hepatocellular carcinoma (HCC), lung adenocarcinoma (LUAD), and ovarian cancer (OC) cells with cisplatin-induced DNA damage were treated with lactate at a concentration gradient, Endothelial cell-specific molecule 1 (ESM1) shRNA, ESM1 overexpression plasmid, or the Protein Kinase B (AKT) Serine/Threonine Kinase 1 (Akt1) inhibitor LY294002. Analysis of tumor patient samples further validates the negative correlation between ESM1 and CD8+ T cell levels in cancer patients. In summary, lactate activates the Akt1-Murine Double Minute 2 (MDM2)-p53 pathway via ESM1 to suppress DDR, while the reduction of DDR-generated dsDNA inactivates the cyclic GMP-AMP synthase-Stimulator of Interferon Genes (cGAS-STING) pathway, thereby inhibiting CD8+ T cell immune infiltration.

However, PRDX4 overexpression showed opposite effects, which were partly reversed by the ferroptosis inhibitor, ferrostatin-1 and the inducer erastin. Most crucially, PRDX4 depletion-mediated inactivation of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway could be rescued by 740 Y-P (a PI3K activator), whereas PRDX4 overexpression triggered the activation of the PI3K/AKT signaling pathway, which could be reversed by the PI3K inhibitor LY294002. Collectively, the data suggest that PRXD4 suppresses ferroptosis in ESCC cells by activating the PI3K/AKT signaling pathway, suggesting that targeting PRDX4 may be a novel strategy for treating patients with ESCC.

Importantly, these oncogenic effects were effectively reversed by GTSE1 knockdown or PI3K inhibition with LY294002, validating the pathway's functional significance. The MYBL2-GTSE1 axis promotes LSCC progression through PI3K/AKT-mediated metabolic reprogramming, representing a promising therapeutic target.

H3K18la enhances the malignant behavior of GC cells through activation of the POM121/PI3K/AKT pathway. These findings provide new insights into the role of histone lactylation in GC progression and suggest that targeting the H3K18la-POM121-PI3K/AKT axis may represent a potential therapeutic avenue worthy of further investigation.

We found that the PI3K inhibitor LY294002 counteracted BRIP1-driven oncogenic effects, which was evidenced by restored expression of key regulators governing apoptosis, cell cycle progression, and EMT, in addition to suppressed proliferation in GC cells. BRIP1 is postulated to function upstream of the PI3K/Akt signaling cascade. This study establishes a risk scoring model and identifies BRIP1 as a potential prognostic marker for GC.

IKZF3 drives GC progression and oxaliplatin resistance by activating PI3K/AKT/mTOR signaling. It is a potential prognostic biomarker and therapeutic target, supporting further development of LY294002 and Iberdomide for GC treatment.

These protective effects were abolished by PI3K inhibitor LY294002. Nodakenin exerted neuroprotective effects against cerebral I/R injury by regulating the PI3K/AKT/NF-κB pathway to reduce neuroinflammation, oxidative stress and ferroptosis. These findings identify Nodakenin as a promising candidate for limiting secondary injury after ischemic stroke.

RHBDD1 facilitates CC progression by promoting proliferation, EMT, migration, invasion, and tumorigenesis through activation of the EGFR/PI3K/AKT pathway, likely via direct receptor-level interaction. Targeting this regulatory node may offer a promising therapeutic approach for CC.

These findings position MEK1/2 and PI3K as promising therapeutic nodes for managing cutaneous HSV-1 infections. This host-directed dual-pathway inhibition may therefore help reduce recurrent orolabial HSV-1 lesions.