PI3K/AKT信号通路与白血病

白血病（leukemia）是一种源于骨髓的造血干细胞恶性增殖性疾病。PI3K/AKT信号通路是一种胞内传导的信号通路,与肿瘤细胞生存息息相关。本文就PI3K/AKT信号通路与白血病的相关性进行综述。     

卵巢上皮性癌中p-AKT、PI3K和PTEN蛋白的表达及意义

目的：探讨磷酸化AKT（p-AKT）、3-羧基磷脂酰肌醇激酶（PI3K）与张力蛋白同源的第10染色体丢失的磷酸酶基因（ PTEN）在卵巢上皮性癌中的表达,分析它们之间的关系及其与卵巢上皮性癌患者预后的关系。方法应用免疫组织化学方法,检测10例正常卵巢组织,20例卵巢良性上皮性肿瘤,60例卵巢上皮性癌组织中p-AKT、PI3K和PTEN的表达。结果 P-AKT和PI3K在正常卵巢组织、卵巢良性上皮性肿瘤中的阳性表达显著低于卵巢上皮性癌组织,而PTEN蛋白在卵巢上皮性癌组织中的表达显著低于正常卵巢组织、良性上皮性肿瘤（ P均＜0．01）。P-AKT、PI3K和PTEN表达与临床分期、病理分级、是否存在淋巴结转移及远处转移有关（ P ＜0．01）,与年龄、病理类型及是否伴有腹水无关（ P ＞0．05）。 P-AKT和PI3K在卵巢上皮性癌中的表达呈正相关（ r ＝0．552, P ＜0．01）,P-AKT和PTEN卵巢上皮性癌中的表达呈负相关（ r ＝-0．497, P ＜0．01）,PI3K和PTEN卵巢上皮性癌中的表达呈负相关（ r ＝-0．535, P ＜0．01）。结论 P-AKT、PI3K的过表达伴随PTEN表达缺失参与卵巢上皮性癌的发生发展。     

PI3K/Akt/mTOR信号通路与肿瘤

在近年来的肿瘤治疗中,靶向生物治疗逐渐成为研究的热点。该文就磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白[phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt)/the mammalian target of Rapamycin(mTOR),PI3K/Akt/mTOR]信号通路予以综述,重点包括PI3K/Akt/mTOR信号转导在肿瘤机制中作用以及肿瘤治疗过程中耐药性方面的关系等。     

基于PI3K/Akt/mTOR信号通路的自噬调节剂研究进展

细胞自噬与多种疾病的发生密切相关.在神经退行性疾病、代谢性疾病、遗传性肝脏疾病、心脏疾病及肿瘤等疾病中均出现异常自噬.通过小分子药物调节相关疾病中的自噬功能,有可能成为疾病治疗的新策略.目前研究阐明,PI3K/Akt/mTOR信号通路与自噬的发生关系密切,小分子药物通过干扰该通路中相关激酶来调控细胞自噬.本文针对PI3...     

PI3K/AKT/mTOR信号通路参与自身免疫性

自身免疫性疾病（autoimmune disease,AD）是机体因自身抗原免疫耐受障碍而对自身抗原产生免疫反应,从而引起机体组织损伤的一类疾病。近年研究发现,磷脂酰肌醇-3-激酶/蛋白激酶B/雷帕霉素靶蛋白（phosphatidylin ositol 3-kinase/protein kinase B/mechanistic target ofrapamycin kinase,PI3K/AKT/mTOR）信号通路与AD发病密切相关,其主要参与免疫细胞增殖分化、炎性细胞因子分泌、自噬及氧化应激等过程。本文重点概述PI3K/AKT/mTOR信号通路参与AD发病机理的研究进展。     

肿瘤干细胞信号通路(PI3K/AKT)研究与进展

肿瘤干细胞是一组存在于肿瘤细胞中可有效躲避放化疗治疗并具有较强增殖与分化能力的小部分细胞亚群,是肿瘤发生发展、产生耐药、治疗后复发的主要原因,根除肿瘤干细胞是彻底治愈肿瘤的一大关键.PI3K/AKT是与肿瘤细胞的多种生命活动密切相关的一条信号通路,介导肿瘤细胞的增殖、迁移、转移以及自我更新等生命活动,在大多数肿瘤细胞中...     

PI3K/Akt/mTOR信号通路与结直肠恶性肿瘤

结直肠癌(colorectal cancer,CRC)是世界大多数地区最常见的恶性肿瘤之一。它的发展是一个多步骤过程,以改变正常细胞的分子信号为启动点,促进细胞发展,最终产生一种表型改变的恶性转化细胞。已有报道指出磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白[phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt)/the mammalian target of Rapamycin(mTOR),PI3K/Akt/mTOR]信号通路与结直肠恶性肿瘤产生有紧密的联系。也有报道证明约60%~70%的结直肠癌患者存在Akt信号的活化及PTEN的表达受损,进而说明PI3K/Akt/mTOR信号通路抑制药可以作为恶性肿瘤治疗的潜在靶点。近年来,PI3K/Akt/mTOR信号通路受到越来越多的关注,在不同的实验模型中利用针对这条通路的天然及合成药物来降低恶性肿瘤负荷。将近年来PI3K/Akt/mTOR信号通路在结直肠恶性肿瘤中的研究做一综述,并就今后结直肠恶性肿瘤中该通路可能的研究方向进行展望。     

PI3 K/Akt信号通路与缺血性中风的相关性研究进展

PI3K/Akt信号转导通路是存在于生物体内一种重要的信号转导途径,参与多种生理功能的调节.近年来研究发现,PI3K/Akt信号通路参与了缺血性中风的病理过程,并在其中发挥了一定的保护作用,被认为是预防该病重要的级联反应通路之一,串扰在细胞凋亡、自噬、氧化应激及炎性反应等多种关键环节中,且处于核心地位,与缺血性中风的严...     

PI3K/AKT信号通路在银屑病发病机制中的研究进展

银屑病是一种免疫介导的多因素炎症性皮肤病,以表皮角质形成细胞异常增殖、毛细血管扩张、中性粒细胞浸润为主要病理表现。磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase,PI3K）/蛋白激酶B（protein kinase B,AKT）信号通路在表皮细胞增殖、细胞自噬、血管生成、脂质代谢等过程中...     

苦瓜皂苷对糖尿病肾病PI3K/Akt信号通路的影响

目的 探讨苦瓜皂苷对糖尿病肾病(DN)PI3K/Akt信号通路的影响。方法 50只雄性小鼠采用高脂饮食联合链尿佐菌素85mg/kg腹腔注射建立DN模型。除模型组(A组)10只外,DN小鼠采用格列本脲0.16g-1·kg-1·d-1灌胃(B组,10只)及30、60、120mg-1·kg-1·d-1苦瓜皂苷灌胃(D1、D2、D3组,各10只)连续治疗14d;另设10只雄性小鼠为空白对照(C组)。采用组织芯片联合免疫组化观察小鼠肾脏组织中p-PI3Kp85(Y458)、p-Akt(Ser473)和负调控基因PTEN表达;Western blot检测小鼠肾脏组织中p-PI3Kp85(Y458)、p-Akt(Ser473)和PTEN蛋白的表达。结果p-PI3Kp85(Y458)和p-Akt(Ser473)主要分布在肾小管上皮细胞质中,PTEN主要分布在肾小管上皮细胞核中。与C组相比,A组p-Akt(Ser 473)和p-PI3Kp85(Y458)表达水平升高,而PTEN表达水平降低(P<0.05)。与A组相比,B组及D2、D3组p-PI3Kp85(Y458)和p-Akt(Ser 473)表达水平均降低(P<0.05),B组和D3组PTEN表达水平升高(P<0.05)。结论 苦瓜皂苷可以上调PTEN的表达,抑制PI3K/Akt通路的活化,对DN小鼠的肾脏有保护作用。     

PTEN、PI3K和miR-21在胃癌中的表达及相关性研究

目的 探讨第10号染色体同源丢失性磷酸酶-张力蛋白基因(PTEN)、磷脂酰肌醇3-激酶(PI3K)和miR-21在胃癌中的表达及相互关系.方法 收集77例胃癌患者手术切除的胃癌组织及胃黏膜组织标本,应用荧光定量RT-PCR及Western blot-ting技术检测miR-21、PTEN和PI3K蛋白的表达水平,并分析miR-21与PTEN/PI3K信号通路之间的关系,以及与临床病理参数之间的相关性.结果 胃癌组织中miR-21及PI3K蛋白的表达水平均明显高于胃黏膜组织(P<0.05),PTEN蛋白的表达水平则明显降低(P<0.05);胃癌组织中PTEN蛋白的表达与肿瘤浸润深度、分化、TNM分期、淋巴转移有关(P<0.05),PI3K蛋白的表达与肿瘤淋巴转移和TNM分期有关(P<0.05);胃癌组织中PTEN蛋白的相对表达水平与miR-21和PI3K蛋白表达呈负相关(r=-0.428,P<0.05;r=-0.517,P<0.05).结论 miR-21可能通过抑制PTEN,激活P13K信号通路参与胃癌的发生发展.     

PI3K/Akt/mTOR信号传导通路与前列腺癌关系的研究进展

前列腺癌是威胁中老年男性健康的常见肿瘤,成为男性癌症死因的第二位。 PI3K/Akt/mTOR信号通路能够通过维持细胞生存、抑制细胞凋亡、促进细胞周期运行及血管生成等促进前列腺癌病程发展。本文综合国内外文献,阐述PI3K/Akt/mTOR信号通路在前列腺癌发生发展中的作用以及和通路相关的药物治疗进展。     

Arctigenin promotes bone formation involving PI3K/Akt/PPARγ signaling pathway

This study investigated the mechanisms through which arctigenin promotes osteogenesis. Bone marrow mesenchymal stem cells (BMSCs) from ovariectomized (OVX) rats were differentiated into osteoblasts, and osteogenesis was evaluated via Alizarin Red S (ARS) staining and alkaline phosphatase (ALP) measurements in cultured BMSCs. The levels of phosphorylated AKT serine/threonine kinase 1 (p‐Akt), and peroxisome proliferator‐activated receptor gamma (PPARγ) expression were quantified by Western blot analysis. The levels of urine calcium (U‐Ca), urine phosphorus (U‐P), serum ALP, and bone mineral density (BMD) of OVX rats were assessed in vivo. The results showed that treatment with arctigenin in rat BMSCs enhanced mineralization, increased ALP activity, increased the expression of Akt and p‐Akt, and decreased PPARγ expression, consistent with its ability to promote osteoblast differentiation. Furthermore, arctigenin prevented OVX‐induced osteoporosis in rats by increasing BMD and ALP activity and inhibiting the loss of Ca and P. In contrast, treatment with LY294002, a selective inhibitor of the phosphatidylinositol 3‐kinase (PI3K), produced the opposite phenotype. These data suggest that the protective effects of arctigenin on BMSCs and OVX rat models result from the induction of osteogenesis involving the PI3K/Akt/PPARγ axis.     

Polystyrene microplastics induce autophagy and apoptosis in birds lungs via PTEN/PI3K/AKT/mTOR

Microplastics (MPs) seriously pollute and potentially threaten human health. Birds are sentinels of environmental pollutants, which respond quickly to contamination events and reveal current environmental exposure. Therefore, birds are good bioindicators for monitoring environmental pollutants. However, the mechanism of lung injury in birds and the role of the PTEN/PI3K/AKT axis are unknown. In this study, broilers treated with different polystyrene microplastics (PS-MPs) (0, 1, 10, and 100 mg/L) were exposed to drinking water for 6 weeks to analyze the effect of PS-MPs on lung injury of broilers. The results showed that with the increase of PS-MPs concentration, malonaldehyde (MDA) content increased, and catalase (CAT) and glutathione (GSH) activity decreased, further leading to oxidative stress. PS-MPs caused the PI3K/Akt/mTOR pathway to be inhibited by phosphorylation, and autophagy accelerated formation (LC3) and degradation (p62), causing autophagy. In PS-MPs exposed lung tissues, the expression of Bax/Bcl-2 and Caspase family increased, and MAPK signaling pathways (p38, ERK, and JNK) showed an increase in phosphorylation level, thus leading to cell apoptosis. Our research showed that PS-MPs could activate the antioxidant system. The antioxidant system unbalance-regulated Caspase family, and PTEN/PI3K/AKT pathways initiated apoptosis and autophagy, which in turn led to lung tissue damage in chickens. These results are of great significance to the toxicological study of PS-MPs and the protection of the ecosystem.     

Resveratrol attenuates intestinal injury in irradiated rats via PI3K/Akt/mTOR signaling pathway

Radiation‐induced enteritis is one of the greatest challenges in radiotherapy. The current study was designed to evaluate the ameliorative effect of resveratrol, which exhibits anti‐inflammatory property, against radiation‐induced intestinal injury in rats and to explore the underlying mechanism. Rats were exposed to a single dose of 5 Gy. Resveratrol (20 mg/kg/day) was orally administered to irradiated rats over 3 weeks. Results showed that resveratrol ameliorated the intestinal oxidative stress parameters; malondialdehyde (MDA) content, glutathione (GSH) level, and catalase (CAT) activity compared to irradiated group. Furthermore, resveratrol reduced the contents of inflammatory cytokines; tumor necrosis factor α (TNF‐α), nuclear factor‐kappa (NF‐κB), and interleukin 1β (IL‐1β) in intestine. Western blotting analysis revealed that resveratrol down‐regulated the proteins expression of phosphoinositide 3‐kinases (PI3K), protein kinase B (Akt) as well as the mammalian target of rapamycin (mTOR) in intestinal tissues of irradiated rats and thus reduced the inflammatory mediator production. These results were confirmed by histopathological investigation. In conclusion, resveratrol attenuated intestinal inflammation following irradiation via modulating PI3K/Akt/mTOR pathway and thereby could be a promising adjuvant in radiotherapy.     

PI3K/AKT信号通路在心房颤动中的研究进展

心房颤动（房颤）作为最常见的快速性心律失常,目前主要的治疗手段为抗凝、控制心室率、维持窦性心律。然而房颤的发生机制尚未阐明,上述治疗仍具有一定的局限性。磷脂酰肌醇3-激酶（PI3K）/蛋白激酶（AKT）信号转导通路是参与房颤发生发展的重要通路,其可以通过介导心房纤维化、炎症反应、氧化应激、神经内分泌功能调节参与房颤发生发展的病理生理过程。深入研究PI3K/AKT信号转导通路在房颤中的作用,可为房颤的预防、治疗及预后评估提供有价值的指导。     

白杨素通过PI3K/AKT信号通路抑制LPS诱导的软骨细胞自噬

Aim To explore the effect of chrysin on chondrocyte autophagy in rat chondrocyte osteoarthritis model induced by lipopolysaccharide and its mechanism. Methods Normal articular cartilage cells of 10 SPF SD rats were isolated and cultured in vitro, and the autophagy of rat chondrocytes was induced by LPS. The experiment was divided into blank control group, LPS group, chrysin (CHR) group and LPS + CHR group, the activity of cells in each group was detected by CCK-8 method, the mitochondrial membrane potential of cells in each group was detected by Rhodaminel23, and the protein expression of PI3K, AKT, p-PI3K, p-AKT, Beclin-1 and LC3 II in cells of each group was detected by reactive oxygen species, Western blot method of DCFH-DA. Results Chrysin could inhibit the autophagy induced by LPS, especially when the concentration of chrysin was 10 mmol · L^-1. Chrysin could inhibit the increase of reactive oxygen species (ROS) induced by LPS induced by LPS, inhibit the decrease of mitochondrial membrane potential after injury, and inhibit the expression of Beclin-1 and LC3 II protein and the phosphorylation of PI3K and AKT. Conclusions Chrysin may inhibit autophagy by inhibiting PI3K/AKT signaling pathway and down-regulating the expression of autophagy proteins Beclin-1 and LC3 II, thus protecting chondrocytes. © 2021 Publication Centre of Anhui Medical University. All rights reserved.