LY294002

KLF13 silencing counteracted the inhibitory effects of FBXW5 depletion on cell proliferation, migration, and invasion, as well as its promotion of ferroptosis, effects that were reversed by LY294002. In conclusion, targeting FBXW5 may serve as a potential therapeutic strategy for BC by modulating the KLF13/PI3K/AKT axis.

Furthermore, TAK-242 or LY294002 further enhanced the inhibitory effects chelidonine of on malignant cell behavior. In conclusion, our findings demonstrate that chelidonine effectively suppresses the malignancy of melanoma cells through the inhibition of TLR4/NF-κB and PI3K/AKT signaling pathways, suggesting its potential as a promising therapeutic agent for melanoma treatment.

Additionally, the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 was used to investigate the involvement of CDK1 in the PI3K/AKT pathway...In conclusion, CACYBP appears to function as a tumor promoter in LUAD, at least in part through CDK1-mediated activation of the PI3K/AKT pathway. These findings suggest that CACYBP could serve as a promising therapeutic target and a novel biomarker for LUAD prognosis.

MV favors BMSCs osteogenic differentiation under high-glucose conditions through the upregulation of miR-10b-5p and the activation of PI3K/Akt signaling.

Moreover, the p53 activator Nutlin-3 A accelerated Nanog degradation, while the p53 inhibitor Pifithrin-α stabilized Nanog...Inhibition of p38 and AKT with SB203580 and LY294002 reduced Nanog expression and partially restored Type II collagen levels...The injected zebrafish exhibited structural defects in craniofacial cartilage, confirming Nanog's involvement in chondrocyte differentiation. These findings suggest that Nanog induces chondrocyte dedifferentiation, and this process can be modulated via the p53/KLF4 and p38/AKT pathways.

PML or SOD3 overexpression remarkably promoted the BMSCs osteoblast differentiation under osteogenic medium, which was reversed by LY294002. PML acts as a significant regulator in the BMSCs osteogenic differentiation by regulating the HIF1AN/HIF1α/SOD3 axis and phosphatidylinositol 3 kinase/ protein kinase B pathway.

The autophagy inhibitors LY294002 and chloroquine significantly increased the lethal effects of Nectin‑4‑MMAE on BxPC‑3 and YAPC cells by inducing apoptosis. When Nectin‑4‑MMAE was combined with autophagy inhibitors, the tumor burden of mice was decreased compared with treatment with either drug alone. The present study confirmed the potent therapeutic effects of Nectin‑4‑MMAE against pancreatic cancer, and its unique antitumor mechanism provides new approaches to treatment.

AKT phosphorylation and MDR1 expression triggered by cisplatin were inhibited by treatment with LY294002, a PI3K/AKT inhibitor. Moreover, treatment with the MDR1 inhibitor, PSC833, inhibited MDR1 expression and increased the cisplatin-induced viability inhibition and cytokeratin 18 fragment release. These findings indicated that scutellarein enhances the anticancer effects of cisplatin by inhibiting the PI3K/AKT-MDR1 signaling pathway in NPC/HK1 cells.

Various monomer components within QFG can bind to MD2 or IL-4R, respectively, thereby inducing macrophages towards an M1-like phenotype through TLR4-mediated NF-κB, MAPK, and PI3K/Akt pathway activation, or inhibiting macrophages towards an M2-like phenotype via IL-4R-mediated JAKs pathway inhibition, ultimately exerting an inhibitory effect on the occurrence and development of CAC.

CA exerts neuroprotective effects in ischemic stroke by inhibiting inflammation and oxidative stress through the PI3K/AKT/NF-κB pathway, suggesting its therapeutic potential for cerebral ischemia and supporting the traditional use of V. dunalianum.

The TFAP4-MCM5 signaling axis promotes GC progression through the PI3K/AKT pathway, suggesting that targeting this axis could provide a potential therapeutic strategy for managing gastric cancer.

On the other hand, the inhibitor of p-AKT, Ly294002, strengthened PFOA's regulatory actions on these factors. Overall, our results suggest that PFOA can lead to liver cell injury by inducing oxidative stress and ferroptosis. The effects are conferred through the regulation of the AKT/GSK3β/β-catenin signaling cascades.

Experimental groups were divided based on the different treatments during resuscitation as follows: (1) hemorrhage: adult male CD-1 mice were subjected to hemorrhage at a mean arterial blood pressure of 35-45 mm Hg for 60 minutes, followed by resuscitation with shed blood and lactated Ringer's solution (n = 13); (2) hemorrhage + irisin: receiving irisin (5 μg/kg; n = 13); (3) hemorrhage + irisin + PI3K inhibitor: receiving both Ly294002 (1 mg/kg, i.v.) and irisin (n = 6); and (4) hemorrhage + irisin + p38 inhibitor: receiving SB202190 (1 mg/kg, i.v.) and irisin (n = 6). SIGNIFICANCE STATEMENT: This study has identified a critical pathway in the regulation of trauma/hemorrhage by using a preclinical trauma model, in which irisin, as a hormone factor, stimulates PI3K and p38 pathways to induce protection against traumatic conditions. The study holds promise for developing a new therapeutic strategy to target irisin and its pathways related to PI3K and p38 to treat trauma and its comorbidities to reduce mortality for clinical implications.

In addition, the effects of EA were abolished by LY294002. EA appeared to improve CI in a rat model of SAH through the activation of the PI3K/AKT pathway.

These findings indicate that PD15 could trigger apoptosis by suppressing the Akt/GSK3β signaling pathway in HCT116 cells.

However, the LY294002 inhibitor restores SLC7A11 and FTH1 expression while decreasing GPX4 (P<0.001). Our research demonstrated that LOXL2 might protect EC via phosphorylation by activating the PI3K/AKT pathway.

We treated MCF-7 cells with T3 (10 nM) for 1 hour in the presence or absence of inhibitors for αvβ3 integrin (RGD peptide), MAPK (PD98059), PI3K (LY294002), and protein synthesis (cycloheximide [CHX]). In addition, CHX completely abolished T3-induced AREG mRNA expression, indicating that this effect requires prior protein synthesis. The identification that T3 acts through this signaling pathway holds considerable potential for clinical application, as it could lead to the development of specific drugs to block it.

This study presents novel findings elucidating the beneficial effect of REM in ALI. This effect can be attributed to REM's ability to inhibit apoptosis by activating of the PI3K/AKT pathway in endothelial and epithelial cells. Additionally, REM targeted TSPO to regulate this pathway in endothelial cells. These results suggested a potential protective role for REM in ALI/ARDS management.

Fastin-1 protein levels and p-Akt1/Akt1 rate were increased by Akt activator SC79 and were decreased by Akt inhibitor LY294002...In conclusion, silencing Fascin-1 reduced the malignant growth of HCC, and this process was closely related to AKT inactivation. The online version contains supplementary material available at 10.1007/s10616-025-00707-9.

Here, we found that EGCG, similar to LY294002 (a specific inhibitor of phosphatidylinositol 3-kinase [PI3K]), downregulated Akt activation and restored the action of glycogen synthase kinase-3β (GSK-3β), accompanied by TGF-β1-caused changes in hallmarks of EMT such as N-cadherin, E-cadherin, vimentin, and Snail in A549 cells...Furthermore, it was shown that EGCG suppressed TGF-β1-elicited invasive phenotypes of A549 cells, including invading and migrating activities, matrix metalloproteinase-2 (MMP-2) secretion, cell adhesion, and wound healing. In summary, we suggest that EGCG inhibits the induction of EMT by TGF-β1 in NSCLC not only through a Smad-dependent pathway, but also through the regulation of the PI3K/Akt/β-catenin signaling axis.

Songorine, aconitine, and benzoylaconine may inhibit ovarian cancer growth in vivo by blocking the PI3K/AKT signaling pathway. Our findings may provide evidence for the clinical application of the processed products of Aconitum soongaricum Stapf. in ovarian cancer treatment.

Both MEK1/ERK and PI-3 K/Akt SPW play crucial roles in bFGF-mediated HIF-1 activation. BFGF had a notable activation of HIF-1. PI-3 K/Akt and MEK1/ERK SPW worked together to regulate this process by various mechanisms.

Ly294002, a selective phosphatidylinositol 3-kinase (PI3K)/Akt inhibitor, suppressed the β-catenin/TCF4 complex activation and EMT through blocking Akt-mediated GSK-3β inactivation in the "disruption complex" in chronic NaAsO2 exposed DU145 and PC-3 cells...These findings provide evidence that chronic arsenic exposure promotes migration and invasion of prostate cancer cells via an EMT mechanism driven by the AKT/GSK-3β/β-catenin/TCF4 signaling axis. Akt is expected to be a potential therapeutic target for chronic arsenic exposure-mediated prostate cancer metastasis.

Adiponectin (ADN) regulates DNA synthesis, cell apoptosis and cell cycle to participate in the pathology and progression of glioblastoma. Markedly, ADN-mediated TMZ resistance was further attenuated by LY294002, suggesting that ADN activated the Akt/mTOR pathway to induce TMZ resistance in glioblastoma cell lines. In conclusion, ADN activated the Akt/mTOR pathway to facilitate cell cycle, inhibit cell apoptosis and induce TMZ resistance in glioblastoma.

This study presents novel findings elucidating the beneficial effect of REM in ALI. This effect can be attributed to REM's ability to inhibit apoptosis by activating of the PI3K/AKT pathway in endothelial and epithelial cells. Additionally, REM targeted TSPO to regulate this pathway in endothelial cells. These results suggested a potential protective role for REM in ALI/ARDS management.

SS exerted its anti-cervical cancer effects by inhibiting cell proliferation, promoting apoptosis, and inhibiting the PI3K/AKT signaling pathway.

Furthermore, PFBA up-regulated the proliferation-related factors downstream of ERRγ and inhibited by PI3K/Akt inhibitor LY294002, which also suppressed the cell proliferation induced by PFBA. Taken together, the results revealed that PFBA had estrogen effects at the human-related exposure concentration, and demonstrated a new estrogen effects mechanism of PFBA via ERRγ pathway.

PI3K inhibitor LY294002 intervention could reduce the promoting effect of AU on ribosome biogenesis. The above results suggest that AU can improve the injury of nucleus pulposus cells and ECM degradation, and its mechanism of action is related to its activation of the PI3K/mTOR pathway to promote ribosome biogenesis.

We established an in vivo POCD model using isoflurane inhalation anesthesia with exploratory laparotomy...Finally, the PI3K inhibitor, LY294002, reversed the effects of metformin on the levels of PI3K, AKT phosphorylation, and BDNF in vitro cultured HT-22 cells...These results reveal that metformin may alleviate POCD by modulating the PI3K/AKT/BDNF axis. Our study may provide a novel strategy for preventing and treating POCD with this medication.

Anesthetic sevoflurane (Sev) causes cognitive dysfunction and neuronal death when used as an anesthetic during surgical procedures. The PI3K/Akt/mTOR pathway inhibitor LY294002 reversed the ameliorative effects of high-dose GpS on cognitive deficits and cell damage in primary hippocampal neurons in Sev anesthetized rats (p<0.05). We conclude that GpS ameliorates Sev-induced neurotoxicity and cognitive dysfunction by modulating the PI3K/Akt/mTOR pathway and alleviating neuronal apoptosis and oxidative stress.

Our findings provide a novel mechanism by which TRPV4 directly activates Ca2+/FAK/PI3K/AKT/GSK3β pathway and further indirectly enhances the FAK/PI3K/AKT/GSK3β pathway through the promotion and secretion of ECM1 to promote LMS malignant progression. Targeting the TRPV4/FAK axis might be a promising potential strategy for prognosis and treatment of LMS.

The detailed molecular mechanisms were subsequently elucidated, and it was found that miR-155-5p bound with HuR to increase the stability and expression levels of VEGFR2, which further activated the tumor-promoting PI3K/Akt/mTOR signal pathway, and M2-exos-enhanced cancer progression in NSCLC cells were apparently suppressed by downregulating VEGFR2 and PI3K inhibitor LY294002 co-treatment. Taken together, M2-polarized TAMs secreted miR-155-5p-containing exosomes to enhanced cancer aggressiveness of NSCLC by activating the VEGFR2/PI3K/Akt/mTOR pathway in a HuR-dependent manner.

LY294002 further alleviated BCP in rats, while the effects were reversed after treatment with insulin-like growth factor 1 (IGF-1). Both LSW and its active ingredient Bufalin were shown to inhibit the viability and migration of Walker 256 cells and induce apoptosis. Bufalin appears to be the key active ingredient of LSW and exerts its pain-relieving effects by suppressing PI3K/Akt and TRPV1 signaling in BCP.

In addition, luteolin downregulated the expression of p-Akt (Ser473), MDM2, and Bcl-2 but upregulated the expression of p53 and Bax, which was consistent with the effect of LY294002. Luteolin had a good anti-NSCLC effect, and the apoptosis-inducing effect might be related to the Akt/MDM2/p53 signaling pathway.

LY294002 blocked SYK (L) knockdown-induced enhancement of migration and invasion as well as the expression EMT-related markers, whereas IGF-1 rescued the decreased migration, invasion and EMT induced by SYK (S) knockdown. The results suggest that SYK(L) and SYK(S) are involved in the progression of cervical cancer through PI3K/AKT signaling pathway, and may serve as potential targets for clinical treatment of advanced cervical cancer.

Inhibiting PI3K/Akt with LY294002, Capivasertib (AZD5363), or using an inactive Akt mutant significantly increased p35 expression and subsequently enhanced AR stability and activation in PCa cells. Importantly, CDK5 knockdown further reduced PI3K/Akt-inhibition-induced AR and cell viability maintenance, suggesting a compensatory role for CDK5-AR in maintaining cell viability under Akt inhibition. In conclusion, PI3K/Akt inhibition could trigger p35-CDK5-dependent AR activation and cell viability, highlighting p35-CDK5 as a critical link connecting PI3K/Akt inhibition to AR activation and pivotal in PCa cell resistance to PI3K/Akt blockade.

The PI3K inhibitor (LY294002) could reverse the effects of MCM4 on MM cells. MCM4 could substantially prompt the tumor growth of MM in mice through the PI3K/AKT pathway in vivo. In summary, MCM4 prompted the development and metastasis of MM by activating the PI3K/AKT pathway.

Moreover, inhibition of the Akt/mTOR signaling pathway with LY294002 (a PI3K inhibitor) enhanced the protective effect of Lut against Cd-induced cell death by suppressing Cd-induced activation of Akt, mTOR, and eukaryotic initiation factor 4E binding protein 1. The results showed that Lut prevented Cd-induced cell death partly by blocking the Akt/mTOR signaling pathway. Lut may be a potential agent for preventing Cd-induced nerve cell damage and neurodegenerative diseases.

To evaluate the effect of the PI3K/AKT pathway on TNFRSF11B, LY294002, a PI3K/AKT pathway inhibitor, was utilized...In BC, TNFRSF11B exhibits elevated expression levels and has a substantial tumor-promoting role in BC via the PI3K/AKT pathway. Importantly, TNFRSF11B may represent a valuable prognostic tumor marker for BC treatment.

BXD has the effect of inhibiting tumor growth rate and delaying the development of GC. Its mechanism of action may be related to the regulation of PI3K-Akt signaling pathway.

These effects were specific, being significantly hindered by NPS2143 and inhibitors of PI3K (LY294002), AMPKα (Dorsomorphin), mTOR (Torin1), and JAK/TYK (Brepoticinib). The neatly divergent modulation of NLRP3's vs. AIM2's PRR proteins by Aβ•CaSR cues and by Bay11-7082 suggests that, when bacterial or viral DNA fragments are absent, AIM2 might play "anti-inflammasomal" or other roles in HCAs. However, Bay11-7082's no effect on NLRP2 PRR overexpression also reveals that CaSR's downstream mechanisms controlling inflammasomes' sensors are quite complex in HCAs, and hence, given AD's impact on human health, well worth further studies.

Finally, SPAG4-overexpressed CRC cells were treated with LY294002 to validate the inhibition of PI3K/Akt pathway on CRC cell malignant phenotypes...Collectively, SPAG4 plays an oncogenic role in CRC by promoting mitochondrial respiration and aerobic glycolysis through activating the PI3K/Akt signaling. These findings suggest that inhibition of SPAG4-mediated glucose metabolism may represent a potential strategy for the clinical treatment of CRC.