The proteasome inhibitor MG132 confirmed that fisetin accelerates β-catenin and MITF degradation. Additionally, inhibition of the PI3K/AKT pathway by LY294002 or the ERK pathway by PD98059 reversed fisetin's reduction of tyrosinase activity and melanin synthesis, further verifying the participation of these pathways. Computational docking integrated with deep learning-based CNN scoring revealed that fisetin interacts with PKCα, β-catenin, tyrosinase, and TYRP1. Collectively, these findings suggest that fisetin exerts multi-targeted inhibitory effects on melanogenesis, highlighting its potential as a therapeutic and cosmetic agent for hyperpigmentation.

Critically, the use of a PI3K inhibitor (LY294002) demonstrated that the nicotine-induced downregulation of p53 and upregulation of MMP-2, as well as the enhancement of cellular invasion are dependent on PI3K/AKT pathway activation. These findings conclusively demonstrate that nicotine promotes the malignant transformation of HPV-16 positive cervical cancer cells by altering the expressions of MMP-2, p53, Caspase-3, and p21 via the activation of the PI3K/AKT pathway. This highlights the therapeutic potential of targeting this pathway in cervical cancer treatment.

Interventions utilizing a range of inhibitors at the in vitro level, including the PDGFR-β inhibitor AG1296, the PI3K inhibitor LY294002, the AKT inhibitor MK2206, and the FAK inhibitor Y15, demonstrated that E. multilocularis protoscoleces protein (EmP) induces angiogenesis through PDGFR/PI3K/AKT/FAK signaling pathway. Our findings provide new perspectives on how E. multilocularis infection triggers pathological angiogenesis in the host liver, and may provide a novel anti-angiogenic therapeutic strategy against E. multilocularis infection.

When these cancer cells were treated with doxorubicin (ADM) and 5-fluorouracil (5-FU), cell survival rate was determined by MTT, apoptosis by TUNEL, and colony formation by colony formation assay. The cancer cells were treated with the PI3K/Akt pathway inhibitor LY294002, and the expression of drug resistance-related proteins MDR1, MRP1, BCRP, Livin, cIAP1, XIAP, Akt, p-Akt, p65, and p-p65 was detected by Western blotting...AFP regulates the expression of drug resistance-related genes by activating the PI3K/Akt/NF-κB signaling pathway. AFP plays a pivotal role in MDR of cancer cells, the mechanism may be involved in activating the PI3K/Akt/NF-κB signaling pathway.

Our study reveals for the first time that TAX restores osteogenic-adipogenic equilibrium in OP-BMSCs and promotes bone regeneration through PI3K/AKT/PPARγ activation and mitochondrial protection-mediated suppression of necroptosis. These results position TAX as a promising therapeutic candidate for osteoporosis.

Helicobacter rodentium exacerbates anti-NMDAR encephalitis by inducing PI3K/AKT-mediated Tfh/Tfr imbalance, highlighting a potential therapeutic target in autoimmune encephalitis.

Treatment with the PI3K inhibitor LY294002 effectively inhibited p-PI3K activation and substantially reduced HER2 expression. Immunohistochemistry (IHC) analysis confirmed a strong positive correlation between changes in HER2 expression and tumor radioactive uptake trends. This study highlights the pivotal role of HER2 as a dynamic biomarker in trastuzumab resistance and supports the integration of molecular imaging into clinical decision-making for personalized therapeutic adjustments in HER2-positive breast cancer.

By inhibiting FAK activation and upregulating PIK3IP1, Ifebemtinib and paclitaxel blocked the PI3K/Akt pathway, effectively suppressing TNBC proliferation and metastasis. Our findings suggest that FAK may serve as a potential therapeutic target for TNBC.

OPN enhances tumor proliferation and survival through mechanistic target of rapamycin and B-cell lymphoma 2 upregulation (e.g., via denticleless E3 ubiquitin protein ligase homolog in hepatocellular carcinoma) and drives metastasis via PI3K/AKT-mediated epithelial-mesenchymal transition and androgen receptor (AR) activation (e.g., via the OPN-RAN-AR axis in pancreatic cancer)...Therapies targeting the OPN-PI3K/AKT axis (e.g., PI3K inhibitors like LY294002) or combination treatments (e.g., with EGFR-TKIs) show promise for reversing drug resistance. Future research should focus on OPN isoform specificity, clinical translation, and interactions with autophagy and long non-coding RNAs to refine precision therapies. This review summarizes recent advances in understanding the molecular mechanisms, therapeutic targets, and clinical challenges of the OPN-PI3K/AKT axis in gastrointestinal tumors, providing a foundation for overcoming resistance and developing precision therapies.

This study shows that BSHT dose-dependently activates the PI3K/Akt pathway, inhibits GSDMD-mediated pyroptosis, and improves mitochondrial dysfunction in PCOS. Its regulation of inflammation, oxidative stress, metabolism, and ovarian function suggests a promising multi-target therapeutic strategy and provides insights for future clinical applications.

WNT5A inhibits steroidogenesis via the PI3K/AKT pathway in granulosa cells. Our findings suggest that increased WNT5A may be attributed to inflammation and may result in endocrine dysregulation in PCOS patients.