pi3k

The provided context includes four original research articles featuring experimental data on the PI3K/AKT signaling pathway across various disease models, including adenomyosis, acute myeloid leukemia, and cancer-related ferroptosis. These studies utilize techniques such as multi-omics, site-directed mutagenesis, and pharmacological inhibition to characterize pathway activation and downstream effects.

PI3K/AKT Signaling in Myometrial Fibrosis of Adenomyosis

Researchers utilized an integrated multi-omics and experimental approach to establish the role of the PI3K/AKT pathway in uterine fibrosis (Direct, High; PMID: 40254638).
* Experimental Models: The study used human myometrial tissue (adenomyotic vs. normal) from 10 patients and primary myofibroblasts isolated from adenomyosis lesions (Direct, High; PMID: 40254638).
* Assays & Results:
* Western blot analysis confirmed significant elevation of phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) in fibrotic adenomyotic myometrium compared to normal controls (Direct, High; PMID: 40254638).
* Immunohistochemical (IHC) staining showed strong p-AKT positivity in stromal cells undergoing metaplasia into myofibroblasts (Direct, High; PMID: 40254638).
* In vitro treatment of myofibroblasts with the dual PI3K/AKT-IN-1 inhibitor significantly reduced cell proliferation (EdU assay) and decreased the expression of fibrosis markers FN1 and Collagen IV (Direct, High; PMID: 40254638).

PI3K/AKT Regulation in Pediatric Acute Myeloid Leukemia (AML)

This study investigated how Quercetin (Que) modulates the miR-224-3p/PTEN axis to inhibit the PI3K/AKT pathway in AML (Direct, High; PMID: 39984900).
* Experimental Models: Human AML cell lines (HL-60, KG-1a) and BALB/c nude mouse xenograft models (Direct, High; PMID: 39984900).
* Assays & Results:
* Quercetin treatment dose-dependently reduced the phosphorylation levels of PI3K and AKT in HL-60 cells (Direct, High; PMID: 39984900).
* The study utilized luciferase reporter assays to prove that miR-224-3p directly targets the 3'-UTR of PTEN, a negative regulator of PI3K/AKT signaling (Direct, High; PMID: 39984900).
* In vivo experiments demonstrated that Quercetin inhibited tumor volume and weight in HL-60 xenografts (Direct, High; PMID: 39984900).

Mechanistic Activation of Protein Kinase B (AKT)

Early experimental work defined the specific phosphorylation requirements for AKT (Protein Kinase B alpha) activation (Direct, High; PMID: 8978681).
* Experimental Models: L6 myotubes and transfected 293 cells stimulated with insulin or IGF-1 (Direct, High; PMID: 8978681).
* Assays & Results:
* Activation of PKBalpha was accompanied by phosphorylation at residues Thr308 and Ser473, both of which were blocked by the PI3K inhibitor wortmannin (Direct, High; PMID: 8978681).
* Mutagenesis experiments (changing Thr308/Ser473 to Ala or Asp) demonstrated that phosphorylation of both residues is critical for achieving high levels of PKBalpha activity (Direct, High; PMID: 8978681).
* The study showed that Thr308 phosphorylation in vivo is not dependent on Ser473 phosphorylation and vice versa (Direct, High; PMID: 8978681).

PI3K-AKT-mTOR Signaling and Ferroptosis Suppression

Experimental evidence suggests that oncogenic PI3K/AKT activation protects cancer cells from oxidative stress-induced ferroptosis (Direct, High; PMID: 33229547).
* Experimental Models: PI3K-mutated breast cancer and PTEN-defective prostate cancer cell lines and xenograft mouse models (Direct, High; PMID: 33229547).
* Assays & Results:
* Inhibition of the PI3K-AKT-mTOR axis sensitized cancer cells to ferroptosis induction (Direct, High; PMID: 33229547).
* The study found that mTORC1-dependent induction of SREBP1 and its target SCD1 (stearoyl-CoA desaturase-1) mediates ferroptosis resistance by producing monounsaturated fatty acids (Direct, High; PMID: 33229547).
* The combination of mTORC1 inhibition with ferroptosis induction resulted in near-complete tumor regression in mouse xenograft models (Direct, High; PMID: 33229547).

What specific PI3K or AKT inhibitors were used in these experimental papers and what were their reported IC50 values?

How did these studies measure the downstream metabolic effects of PI3K/AKT pathway activation?

What specific phosphorylation sites on AKT beyond Ser473 and Thr308 were investigated in the provided research?

Unverified Citations

The following sources failed to support their assigned claims after 3 verification rounds designed to ensure only high-confidence, relevant references are retained:

• PMID:40254638 — These studies utilize techniques such as multi-omics, site-directed mutagenesis, and pharmacological inhibition to chara...
  Failed: entities — The paper utilizes multi-omics and pharmacological inhibition but does not employ site-directed mutagenesis.
  Possible alternatives (unverified): PMID:18794884 (61% topic match)
• PMID:39984900 — These studies utilize techniques such as multi-omics, site-directed mutagenesis, and pharmacological inhibition to chara...
  Failed: mechanism,entities — The paper does not utilize multi-omics or site-directed mutagenesis; it uses standard cell/molecular assays and pharmacological inhibition.
  Possible alternatives (unverified): PMID:18794884 (61% topic match)
• PMID:8978681 — These studies utilize techniques such as multi-omics, site-directed mutagenesis, and pharmacological inhibition to chara...
  Failed: mechanism — The paper utilizes site-directed mutagenesis and pharmacological inhibition (wortmannin) but does not utilize multi-omics.
  Possible alternatives (unverified): PMID:18794884 (61% topic match)
• PMID:33229547 — These studies utilize techniques such as multi-omics, site-directed mutagenesis, and pharmacological inhibition to chara...
  Failed: mechanism — The paper utilizes pharmacological inhibition and genetic ablation but does not utilize multi-omics or site-directed mutagenesis.
  Possible alternatives (unverified): PMID:18794884 (61% topic match)