LY294002, a well-known PI3K signaling pathway inhibitor, is the first synthetic PI3Kα, δ and β inhibitor with IC50 of 500nM, 570nM and 970nM, respectively. LY294002 is not exclusively selective for the PI3Ks, and could in fact act on other lipid kinases and additional apparently unrelated proteins[1]
When LY294002 was added to NPC cells with different concentrations, levels of phosphorylation (S473) Akt were decreased in treated NPC cells, exhibiting a dose-response effect. LY294002 markedly inhibited NPC CNE-2Z cell growth, proliferation, and induced apoptosis in vitro and in vivo[2]. The PI3k/AKT pathway is constitutively activated in a majority of human pancreatic cancer cell lines and the pathway is a promising target for therapeutic intervention. LY294002 produce apoptosis and antiproliferative effects on pancreatic carcinoma cells in vivo and in vitro[3]
LY294002(1.2 mg/kg) was given together with leptin (60 µg/kg) once daily for 14 days via the intraperitoneal (i.p.) route. The result found that body weight in leptin+LY294002-treated rats decreased significantly and STEH was higher (p < 0.001). Ratio of testicular phosphor-Akt/total Akt was significantly higher in leptin+LY294002-treated rats (p < 0.001). The adverse effects of leptin were prevented by concurrent administration of LY294002, suggest the potential involvement of the PI3K signaling pathway in leptin-induced detrimental effects on spermatozoa[4]
LY294002是一种著名的PI3K信号通路抑制剂，是第一个具有IC50分别为500nM、570nM和970nM的合成PI3Kα、δ和β抑制剂。LY294002并不完全选择性地作用于PI3Ks，并且实际上可能对其他脂质激酶和额外看似无关的蛋白质产生影响。
当不同浓度的LY294002添加到NPC细胞中时，处理后的NPC细胞中磷酸化（S473）Akt水平降低，呈现剂量反应效应。LY294002显著抑制了NPC CNE-2Z细胞在体外和体内的生长、增殖，并诱导凋亡[2]。PI3k/AKT通路在大多数人类胰腺癌细胞系中被恒定激活，该通路是治疗干预的有前途靶点。LY294002对体内和体外的胰腺癌细胞产生凋亡和抗增殖作用[3]。
在腹腔注射途径下，每天给予LY294002（1.2毫克/千克）和瘦素（60微克/千克），连续14天。结果发现，在接受瘦素+LY294002处理的大鼠中，体重显著降低，并且精子头部顶端反应时间更长（p[4]。
References:
[1]. Gharbi SI, Zvelebil MJ, et al. Exploring the specificity of the PI3K family inhibitor LY294002. Biochem J. 2007 May 15;404(1):15-21.
[2]. Jiang H, Fan D, et al. Phosphatidylinositol 3-kinase inhibitor (LY294002) induces apoptosis of human nasopharyngeal carcinoma in vitro and in vivo. J Exp Clin Cancer Res. 2010 Apr 22;29(1):34.
[3]. Bondar VM, Sweeney-Gotsch B, et al. Inhibition of the phosphatidylinositol 3'-kinase-AKT pathway induces apoptosis in pancreatic carcinoma cells in vitro and in vivo. Mol Cancer Ther. 2002 Oct;1(12):989-97. PMID: 12481421.
[4]. Almabhouh FA, et al. LY294002, a PI3K pathway inhibitor, prevents leptin-induced adverse effects on spermatozoa in Sprague-Dawley rats. Andrologia. 2019 Apr;51(3):e13196.