- |||||||||| sirolimus / Generic mfg.
Journal: Neuroligin 3 Regulates Dendritic Outgrowth by Modulating Akt/mTOR Signaling. (Pubmed Central) - Dec 22, 2019
In conclusion, our results suggest that NL3 regulates neuronal morphology, especially dendritic outgrowth, by modulating the PTEN/Akt/mTOR signaling pathway, probably via MAGI-2. Thereby, this study provides a new link between NL3 and neuronal morphology.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: C16 Peptide Promotes Vascular Growth and Reduces Inflammation in a Neuromyelitis Optica Model. (Pubmed Central) - Dec 22, 2019
A total of 150 rats were divided into five groups: a control untreated group (n = 18) and four test groups (n = 33 per group) including vehicle-treated control, C16, Tie2 kinase inhibitor + C16, and PI3K/Akt inhibitor LY294002 + C16...In addition, activation of the αvβ3 integrin axis and Tie2 kinase promoted PI3K/Akt signaling. Our study showed that the Tie2-PI3K/Akt, Tie2 integrin, and integrin-PI3K/Akt signaling pathways regulate C16 peptide function in vascular growth and stabilization as well as inflammation in NMO.
- |||||||||| Xalkori (crizotinib) / Pfizer
Journal: Crizotinib and PARP inhibitors act synergistically by triggering apoptosis in high-grade serous ovarian cancer. (Pubmed Central) - Dec 22, 2019
The FDA has approved the PARP inhibitor olaparib (Lynparza™) as maintenance treatment after first-line platinum-containing chemotherapy and olaparib, niraparib (Zejula™) and rucaparib (Rubraca™) are approved as maintenance therapies in the recurrent, platinum-sensitive setting; nevertheless, development of resistance limits their efficacy...Carboplatin, olaparib, niraparib, the PI3K inhibitor LY294002 and the c-Met inhibitor crizotinib were used for this investigation...Crizotinib together with either of the PARP inhibitors was more strongly synergistic than combinations with a PARP inhibitor and carboplatin or the PI3K inhibitor. Sequential combination of crizotinib and a PARP inhibitor resulted in activation of ATM/CHK2 and inhibition of c-Met pathways, contributing to a decrease in RAD51 levels and induction of caspase-3 dependent apoptotic cell death and suggesting that the combination of crizotinib with a PARP inhibitor may be considered and further explored as a new therapeutic strategy in HGSOC.
- |||||||||| quercetin (LY294002) / Eli Lilly, lithium / Generic mfg.
Journal, IO Biomarker: Induced pluripotent stem cell-derived conditional medium promotes Leydig cell anti-apoptosis and proliferation via autophagy and Wnt/β-catenin pathway. (Pubmed Central) - Dec 21, 2019
Meanwhile, iPS-CM could improve the medium testosterone levels and up-regulation of LHCGR, SCARB1, STAR, CYP11A1, HSD3B1, CYP17A1, HSD17B3 and SF-1 in H O -induced ILCs. In conclusion, iPS-CM could reduce H O -induced ILC apoptosis through the activation of autophagy, promote proliferation through up-regulation of Wnt/β-catenin pathway and enhance testosterone production through increasing steroidogenic enzyme expressions, which might be used in regenerative medicine for future.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Gastrin-releasing peptide receptor gene silencing inhibits the development of the epithelial-mesenchymal transition and formation of a calcium oxalate crystal in renal tubular epithelial cells in mice with kidney stones via the PI3K/Akt signaling pathway. (Pubmed Central) - Dec 21, 2019
After treatment of shGRPR-1 and shGRPR-1 + LY294002, levels of urinary oxalate and urinary calcium in the serum, as well as positive rate of GRPR, became relatively low, levels of E-cadherin enhanced, whereas levels of Akt, PI3K, GRPR, extents of PI3K and Akt phosphorylation, α-SMA, Vimentin and FSP-1, OPN, MCP-1, and CD44 decreased and a number of crystals reduced. Taken together, we conclude that GRPR gene silencing suppresses the development of the EMT and formation of the calcium oxalate crystal in renal TECs of kidney stones through the inactivation of the PI3K/Akt signaling pathway.
- |||||||||| Journal: Autophagy as a molecular target for cancer treatment. (Pubmed Central) - Dec 20, 2019
In this sense, we also review the shared regulatory pathways that play a role in autophagy and malignant transformation. Finally, anti-cancer therapeutic agents used as either inhibitors or inducers of autophagy have been discussed.
- |||||||||| quercetin (LY294002) / Eli Lilly, Faslodex (fulvestrant) / AstraZeneca, flutamide / Generic mfg.
Journal: Dehydroepiandrosterone Prevents HO-Induced BRL-3A Cell Oxidative Damage through Activation of PI3K/Akt Pathways rather than MAPK Pathways. (Pubmed Central) - Dec 20, 2019
These effects of DHEA were not observed when the cells were pretreated with known antagonists of sex hormones (Trilostane, Flutamide, or Fulvestrant)...These effects of DHEA were abolished when the cells were pretreated with the PI3K inhibitor LY294002...In conclusion, our data demonstrate that DHEA protects BRL-3A cells against HO-induced oxidative stress and apoptosis through mechanisms that do not involve its biotransformation into steroid hormones or the activation of sex hormone receptors. Importantly, the protective effect of DHEA on BRL-3A cells was mainly associated with PI3K/Akt signaling pathways, rather than MAPK signaling pathways.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal, IO Biomarker: Mytoxin B and Myrothecine A Induce Apoptosis in Human Hepatocarcinoma Cell Line SMMC-7721 via PI3K/Akt Signaling Pathway. (Pubmed Central) - Dec 20, 2019
Moreover, the expression levels of caspases-3, -8, and -9, and cleaved caspases-3, -8, and -9 were all upregulated in both mytoxin B and myrothecine A-treated cells in Western blot analysis, which indicated that both compounds might induce SMMC-7721 cells apoptosis through not only the death receptor pathway but also the mitochondrial pathway. Finally, mytoxin B and myrothecine A were found to reduce the activity of PI3K/Akt signaling pathway that was similar to the effect of LY294002 (a potent and specific PI3K inhibitor), suggesting that both mytoxin B and myrothecine A might induce SMMC-7721 cells apoptosis via PI3K/Akt pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Clinical, Journal: The efficacy and potential mechanism of cnidium lactone to inhibit osteoclast differentiation. (Pubmed Central) - Dec 19, 2019
Furthermore, cnidium lactone inhibited the expression of c-Fos and NFATc-1 with dose-dependently and enhanced by SB203580 and LY294002. In conclusion, cnidium lactone inhibits osteoclast differentiation through p38 MAPK and PI3K-Akt signalling pathway/c-Fos/NFATc1 signalling pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly, Tamoxis (tamoxifen) / Bioprofarma, U0126 / Promega
Journal: Fibrauretine reduces ischemia/reperfusion injury via RISK/eNOS activation. (Pubmed Central) - Dec 8, 2019
It is suggested that eNOS plays an important role in the protective effect of fibrauretine on the heart. Therefore, the results of this study show that the protective effect of fibrauretine on myocardial I/R injury is closely associated with eNOS expression, GR/ER-induced Akt phosphorylation and ERK1/2 activation.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: NCAPG Promotes The Proliferation Of Hepatocellular Carcinoma Through PI3K/AKT Signaling. (Pubmed Central) - Dec 8, 2019
LY294002, a PI3K inhibitor, could eliminate the NCAPG role of promoting HCC cell proliferation and reducing HCC cell apoptosis, while 740Y-P, a PI3K activator, contributed to the opposite effect. NCAPG functions as an oncogene in HCC and plays a role in promoting cell proliferation and antiapoptosis through activating the PI3K/AKT/FOXO4 pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: The Cytoplasmic Expression Of CLDN12 Predicts An Unfavorable Prognosis And Promotes Proliferation And Migration Of Osteosarcoma. (Pubmed Central) - Dec 8, 2019
The results also demonstrated that the overexpression of CLDN12 increased the activation of Thr308 site in Akt in fetal osteoblast cells, and the PI3K inhibitor LY294002 partially decreased CLDN12-promoted proliferation and metastasis. In conclusion, the results of the present study indicated that CLDN12 promoted cell proliferation and migration through the PI3K/Akt signaling pathway in osteosarcoma cells, suggesting that CLDN12 may be a potential agent in the treatment of patients with osteosarcoma.
- |||||||||| quercetin (LY294002) / Eli Lilly, U0126 / Promega
Journal: Tanshinone IIA reverses EGF- and TGF-β1-mediated epithelial-mesenchymal transition in HepG2 cells via the PI3K/Akt/ERK signaling pathway. (Pubmed Central) - Dec 8, 2019
Furthermore, western blot analysis confirmed that blocking the function of PI3K/Akt and ERK with LY294002 and U0126 resulted in upregulation of E-cadherin expression, and downregulation of vimentin and Snail expression in EGF- and TGF-β1-treated HepG2 cells. In conclusion, to the best of our knowledge, the results of the present study are the first to indicate that Tan IIA may suppress EGF- and TGF-β1-induced EMT in HepG2 cells by deactivating the PI3K/Akt/ERK pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal, MSi-H Biomarker, PD(L)-1 Biomarker, IO Biomarker: Functional loss of ARID1A is tightly associated with high PD-L1 expression in gastric cancer. (Pubmed Central) - Dec 6, 2019
Loss of ARID1A increased PD-L1 via activating AKT signaling, while LY294002 (PI3K inhibitor) decreased PD-L1 levels...Our results strongly indicate that loss of ARID1A is tightly associated with high PD-L1 expression in GC. These results would increase our understanding of the oncogenic mechanism of PD-L1 regulation in GC, and also help to find the optimal candidates for immunotherapy.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: Formaldehyde induces the apoptosis of BMCs of BALB/c mice via the PTEN/PI3K/Akt signal transduction pathway. (Pubmed Central) - Nov 29, 2019
Following the application of LY294002 to inhibit the PTEN/PI3K/Akt signal transduction pathway, the numbers of cells arrested in the G0/G1 phase were significantly increased in the PI3K inhibitor group compared with the control (P0.05). The results of the present study suggested that the PTEN/PI3K/Akt signal transduction pathway served an important role in the process of FA‑induced apoptosis, which may be associated with regulating the cell cycle; thus, cell proliferation may be affected.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: MICAL1 facilitates breast cancer cell proliferation via ROS-sensitive ERK/cyclin D pathway. (Pubmed Central) - Nov 28, 2019
LY294002 treatment also attenuated the increase in the p-ERK level in MICAL1-overexpressed breast cancer cells. Together, our results suggest that MICAL1 exhibits its effect on proliferation via maintaining cyclin D expression through ROS-sensitive PI3K/Akt/ERK signalling in breast cancer cells.
- |||||||||| quercetin (LY294002) / Eli Lilly, exendin 9-39 / Eiger
Journal: A New Way for Beta Cell Neogenesis: Transdifferentiation from Alpha Cells Induced by Glucagon-Like Peptide 1. (Pubmed Central) - Nov 27, 2019
We concluded that treatment with GLP1 might result in beta cell neogenesis by promoting the transdifferentiation of alpha cells but not by pancreatic acinar cells, ductal cells, or the self-replication of beta cells. The regulation on the GLP1 receptor and its downstream transcription factor PI3K/AKT/FOXO1 pathway, which causes increased pancreatic and duodenal homeobox 1 (Pdx1) and MafA mRNA expression but causes decreased MAFB expression, may be the mechanism involved in this process.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Autophagy Precedes Apoptosis in Angiotensin II-Induced Podocyte Injury. (Pubmed Central) - Nov 27, 2019
The regulation on the GLP1 receptor and its downstream transcription factor PI3K/AKT/FOXO1 pathway, which causes increased pancreatic and duodenal homeobox 1 (Pdx1) and MafA mRNA expression but causes decreased MAFB expression, may be the mechanism involved in this process. These findings suggest that Ang II promotes autophagy in podocytes before apoptosis as an early adaptive cytoprotective mechanism for podocyte survival after Ang II treatment, and the transitional imbalance between autophagy and apoptosis causes podocyte injury.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Expression of Clusterin suppresses Cr(VI)-induced premature senescence through activation of PI3K/AKT pathway. (Pubmed Central) - Nov 24, 2019
Blockage of the PI3K/AKT pathway with its inhibitor LY294002 eliminated the inhibitory effect of CLU on Cr(VI)-induced premature senescence. We concluded that high expression of CLU suppressed Cr(VI)-induced premature senescence through activation of PI3K/AKT pathway, which will provide the experimental basis for the study of Cr(VI)-induced liver cancer, especially for the elucidation of the mechanism of liver cancer cells escaping from senescence.
- |||||||||| dexamethasone / generics
Preclinical, Journal: IGF-1 reverses the osteogenic inhibitory effect of dexamethasone on BMP9-induced osteogenic differentiation in mouse embryonic fibroblasts via PI3K/AKT/COX-2 pathway. (Pubmed Central) - Nov 22, 2019
Glucocorticoid-Induced Osteoporosis (GIOP) is a prevalent clinical complication caused by large dose administration of glucocorticoids, such as Dexamethasone (Dex) and Prednisone...Regarding the inhibitory mechanism, we found that the level of AKT and p-AKT can be decreased by Dex and that Ly294002, the PI3K inhibitor, can block the reversal effect of IGF-1...Our findings indicated that IGF-1 may reverse the osteogenic inhibitory effect of Dex via PI3K/AKT pathway, which may be associated with the up-regulation of COX-2. This study may provide new clinical management strategy for GIOP cases.
- |||||||||| quercetin (LY294002) / Eli Lilly, endurobol (GW501516) / Ligand, GSK
Journal: Ligand-activated PPARδ inhibits angiotensin II-stimulated hypertrophy of vascular smooth muscle cells by targeting ROS. (Pubmed Central) - Nov 21, 2019
The phosphatidylinositol 3-kinase inhibitor LY294002 also inhibited Ang II-stimulated [3H]-leucine incorporation and ROS generation by preventing membrane translocation of Rac1. These observations suggest that PPARδ is an endogenous modulator of Ang II-triggered hypertrophy of VSMCs, and is thus a potential target to treat vascular diseases associated with hypertrophic changes of VSMCs.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Azithromycin promotes alternatively activated macrophage phenotype in systematic lupus erythematosus via PI3K/Akt signaling pathway. (Pubmed Central) - Nov 19, 2019
After inhibiting Akt phosphorylation by LY294002, the down-regulation of CD80, IL-1β, IL-6, and TNF-α caused by azithromycin raised again, meanwhile, the up-regulation of CD206, Arg-1, Fizz-1, and IL-10 due to azithromycin was abolished...Taken together, our data indicated a novel role of azithromycin in alleviating SLE by promoting alternatively activated macrophage phenotype, and the PI3K/Akt signaling pathway was involved. Our findings provide a rationale for further investigation of novel therapeutic strategy for SLE patients.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: TRIM27 promotes the development of esophagus cancer via regulating PTEN/AKT signaling pathway. (Pubmed Central) - Nov 18, 2019
In addition, an AKT inhibitor LY294002 was used to determine the connection between TRIM27 and AKT in ESCC cells...Hence, TRIM27 also participated in the regulation of energy metabolism in ESCC cells. This research not only gained a deep insight into the biological function of TRIM27 but also elucidated its potential target and signaling pathway in human ESCC cells.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Silencing of TRIM11 suppresses the tumorigenicity of chordoma cells through improving the activity of PHLPP1/AKT. (Pubmed Central) - Nov 18, 2019
Further, LY294002, a specific AKT inhibitor, was utilized to examine the connection between TRIM11 and AKT in human chordoma cells...These results suggested that TRIM11 mediated the post-translation modification of PHLPP1 and was a novel component in PHLPP1/AKT signaling pathway in human chordoma cells. Taken together, the present research not only enhanced the understanding of TRIM11 but also indicated its potential target and signaling pathway in human chordoma cells.Trial registration retrospectively registered.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Deoxynivalenol-Induced Cytotoxicity and Apoptosis in IPEC-J2 Cells Through the Activation of Autophagy by Inhibiting PI3K-AKT-mTOR Signaling Pathway. (Pubmed Central) - Nov 18, 2019
With the purpose to explore the relationship between deoxynivalenol (DON)-induced apoptosis and autophagy and provide mechanistic explanations for the toxic effects of DON on IPEC-J2 cells, we determined the cell viability, cell morphology, apoptosis, and autophagy by using autophagy inhibitor 3-methyladenine (3-MA), PI3K pathway inhibitor LY294002, and activator 740Y-P...To conclude, these data reveal that DON may induce cytotoxicity and apoptosis through the activation of autophagy by suppressing the PI3K-AKT-mTOR signaling pathway. This study provides new insights into the mechanisms by which DON incurs cytotoxic effects.
- |||||||||| quercetin (LY294002) / Eli Lilly, Kuvan (sapropterin) / Merck (MSD), BioMarin, Daiichi Sankyo, U0126 / Promega
Journal: Nitric oxide: Is it the culprit for the continued expansion of keloids? (Pubmed Central) - Nov 14, 2019
In this study, we investigated the effect of NO on KDFs proliferation by Sodium Nitroprusside (SNP), an NO donor...U0126 and LY294002, inhibitors of Erk and Akt respectively, block SNP-enhanced KDFs proliferation effectively...Moreover, it decreased the expression of p, a cell cycle inhibitor. Our results reveal that SNP induced KDFs proliferation and loss contact inhibition led to pile up growth via activation of the Erk and Akt pathways, as well as a decreased expression of p. Thus, we speculate that the pathological feature of continuous expansion in keloids is caused by NO-induced KDFs sustained growth.
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