微小RNA-433-3p靶向滑蛋白调控胰腺癌PANC-1细胞恶性生物学行为的研究

目的 探讨微小RNA-433-3p(miR-433-3p)对胰腺癌细胞增殖、侵袭、迁移的影响及其与滑蛋白(SMO)的靶向关系。方法 培养胰腺癌PANC-1细胞、人正常胰腺上皮细胞HPNE。将miR-NC、miR-433-3p mimics、si-NC、si-miR-433-3p、敲低空载Scramble、si-SMO、Vector、SMO过表达(OE-SMO)质粒分别转染至PANC-1细胞,设为miR-NC组、miR-433-3p组、si-NC组、si-miR-433-3p组、Scramble组、si-SMO组、Vector组及SMO组。将Vector、OE-SMO质粒分别转染至miR-433-3p组细胞,设为si-miR-433-3p+Scramble组、si-miR-433-3p+si-SMO组。采用四甲基偶氮唑蓝(MTT)检测细胞增殖能力,Transwell实验检测细胞侵袭、迁移能力,荧光定量聚合酶链反应(RT-PCR)检测细胞SMO基因mRNA及miR-433-3p表达水平,Western blot检测细胞SMO蛋白表达水平,TargetScan在线网站预测miR-433-3p...     

PI3K/AKT信号传导通路与肠道炎症

磷酸肌醇-3激酶(phosphatidylinositol3kinase,PI3K)是生长因子超家族信号传导过程中的重要分子,可被多种细胞因子和理化因素激活,调节多种细胞功能,如凋亡、增殖、代谢、生长转化、膜转运、分泌和趋化等,并在炎症、肿瘤、代谢和心血管疾病的发病机制中起重要作用[1]。炎症性肠     

PI3K/AKT信号通路在非小细胞肺癌中作用的研究进展

肺癌是目前全世界范围内发病率和死亡率均最高的恶性肿瘤.磷酸酰肌醇-3-激酶/蛋白激酶B(PI3K/AKT)信号通路是所有人类癌症中最重要的致癌途径之一,该通路在肿瘤的发生、增殖以及诱导上皮-间质转化(EMT)等方面扮演者重要角色,并且对于肿瘤的获得性耐药也有影响.目前针对PI3K/AKT信号通路在非小细胞肺癌(NSCL...     

miR-21靶向调控PTEN/PI3K/AKT通路对骨肉瘤细胞增殖、侵袭和凋亡的影响

目的 检测微小核糖核酸（micro RNA, miR）-21在人正常骨细胞hFOB1.19与人骨肉瘤细胞系U2OS,Saos-2和MG-63中的表达,并探讨miR-21对骨肉瘤细胞增殖、侵袭和凋亡的影响。方法 实时荧光定量PCR法(real-time fluorescent quantitative PCR, qRT-PCR)检测人正常骨细胞hFOB1.19与人骨肉瘤细胞系U2OS,Saos-2和MG-63中miR-21的表达。选择MG-63细胞随机分为3组,利用脂质体2000分别转染空白对照（control）、阴性对照miR-21-NC及抑制剂组（miR-21-inhibitor）,再通过qRT-PCR法验证转染后MG-63细胞中miR-21表达。CCK-8法检测MG-63细胞增殖能力变化;流式细胞技术检测抑制miR-21表达对MG-63细胞凋亡的影响;Transwell实验检测对MG-63细胞侵袭能力的影响以及采用Western blot检测抑制miR-21表达对MG-63细胞中PTEN,PI3K,AKT及p-AKT蛋白表达的影响。结果 人骨肉瘤细胞系Saos-2,U2OS和MG-...     

MiR-144-3p对口腔鳞癌Cal27细胞增殖、侵袭、凋亡和PTEN/PI3K/AKT信号通路的影响

目的 探讨微小RNA(miR)-144-3p对口腔鳞癌CAL27细胞增殖、侵袭和凋亡的影响及其机制.方法 将体外培养的CAL27细胞分为miR-144-3p模拟物(mimics)组、mimics阴性对照(NC-mimics)组、miR-144-3p抑制剂(inhibitor)组、inhibitor阴性对照(NC-inh...     

FOXN2通过PI3K/AKT信号通路对肾癌细胞增殖、凋亡的影响

目的 研究FOXN2通过PI3K/AKT信号通路对肾癌增殖、凋亡的影响.方法 实验分FOXN2过表达组、空载体对照组、对照组三组;检测FOXN2在人正常肾上皮细胞HK-2和肾癌细胞786-O中的表达;检测FOXN2过表达组、空载体对照组、对照组细胞的增殖情况和凋亡情况;检测FOXN2过表达组、空载体对照组、对照组细胞P...     

miR-32-5p靶向FOXN3调控EMT通路影响子宫内膜癌细胞迁移和侵袭

目的 研究miR-32-5p对子宫内膜癌细胞迁移和侵袭的影响和潜在机制.方法 以人正常子宫内膜上皮细胞hEEC为对照,qRT-PCR和Western blot检测子宫内膜癌细胞系Ishikawa、HEC-1A和JEC中miR-32-5p和FOXN3的表达;在Ishikawa细胞中高表达FOXN3和敲减miR-32-5p...     

长链非编码RNA SNHG1在子宫内膜癌中的表达及调控PI3K/AKT信号通路的研究

目的 研究长链非编码RNA小核仁RNA宿主基因1(lncRNA SNHG1)在子宫内膜癌组织中的表达及临床意义,并探讨SNHG1在子宫内膜癌中的生物学功能.方法 应用实时荧光定量PCR(qRT-PCR)检测SNHG1在54例子宫内膜癌组织和癌旁组织中的表达水平,并分析子宫内膜癌组织中SNHG1的表达水平与患者临床病理参...     

PI3K/AKT信号通路与缺血性脑损伤引起的细胞凋亡研究进展

PI3K/AKT信号通路是细胞内调控信号转导的一个重要途径,其组成较为复杂,参与细胞增殖、凋亡、代谢等活动。缺血性脑损伤是一个复杂的病理过程,而细胞凋亡在此过程中发挥重要作用。PI3K/AKT信号通路是细胞存活的关键通路,在缺血性脑损伤、神经退行性疾病及肿瘤等诸多疾病中起调控作用。因此,研究该通路并探讨其在缺血性脑损伤中的作用对进一步探寻此类疾病的治疗具有重要意义。     

苏芬太尼通过PI3K/Akt信号通路对肺癌A549细胞增殖、凋亡、迁移和侵袭的影响

目的 探讨苏芬太尼对人肺癌A549细胞增殖、凋亡、迁移和侵袭的影响及对PI3K/Akt信号通路的调控作用.方法 采用不同浓度的苏芬太尼干预肺癌A549细胞,CCK-8法检测苏芬太尼对A549细胞活力的影响,流式细胞术检测苏芬太尼对A549细胞凋亡的影响,Transwell实验检测苏芬太尼对A549细胞迁移和侵袭能力的影...     

PI3K/AKT signaling pathway and cancer: an updated review

Abstract

Despite development of novel agents targeting oncogenic pathways, matching targeted therapies to the genetic status of individual tumors is proving to be a daunting task for clinicians. To improve the clinical efficacy and to reduce the toxic side effects of treatments, a deep characterization of genetic alterations in different tumors is required. The mutational profile often evidences a gain of function or hyperactivity of phosphoinositide 3-kinases (PI3Ks) in tumors. These enzymes are activated downstream tyrosine kinase receptors (RTKs) and/or G proteins coupled receptors (GPCRs) and, via AKT, are able to induce mammalian target of rapamycin (mTOR) stimulation. Here, we elucidate the impact of class I (p110α, β, γ, and δ) catalytic subunit mutations on AKT-mediated cellular processes that control crucial mechanisms in tumor development. Moreover, the interrelation of PI3K signaling with mTOR, ERK, and RAS pathways will be discussed, exploiting the potential benefits of PI3K signaling inhibitors in clinical use.     

过表达乙酰肝素酶对胆囊癌细胞增殖及PI3K/AKT信号通路的影响

目的 探讨过表达乙酰肝素酶(HPSE)对胆囊癌细胞系GBC-SD细胞增殖及磷脂酰肌醇3-激酶/蛋白质丝氨酸苏氨酸激酶(PI3K/AKT)信号通路的影响。方法 构建HPSE真核表达载体,然后获得转基因过表达HPSE的胆囊癌细胞株GBD-SD。通过实时荧光定量聚合酶链反应(qRT-PCR)和Western blot分析GBC-SD和GBD-SD中HPSE mRNA和蛋白表达。通过集落形成实验、MTT来评估各组细胞的增殖情况。采用Western blot分析PI3K/AKT信号通路相关蛋白(p-PI3K、PI3K、p-AKT和AKT)的水平。结果 成功转染后的GBD-SD中HPSE mRNA水平和蛋白水平升高,差异有统计学意义(P<0.01)。与正常表达HPSE的GBC-SD相比,过表达HPSE的GBD-SD细胞光密度(OD)值和集落形成能力提高,差异有统计学意义(P<0.05)。Western blot检测结果显示,与GBC-SD细胞相比,过表达HPSE的GBD-SD组细胞p-AKT、p-PI3K蛋白表达水平、p-AKT/AKT值和p-PI3K/PI3K值增加,差异有统计学意义...     

PI3K/AKT信号通路在急性白血病中调控机制的初步研究

本研究探讨PI3K/AKT通路中的PTEN、CCND1、mTOR、RICTOR、FOXO1基因在急性髓系白血病(AML)、急性淋巴细胞白血病(ALL)患者中与正常人中表达的差异,以期查明PI3K/AKT通路在白血病中是否存在通路失调。随机收集16例骨髓标本,其中白血病12例(AML 6例,ALL 6例),正常骨髓标本4例。用实时定量RT-PCR方法检测PI3K/AKT通路中的PTEN、CCND1、mTOR、RICTOR、FOXO1基因的表达变化;以管家基因GAPDH为内参,按2-△△Ct法计算目的基因相对表达量。结果表明:PTEN、mTOR、RICTOR在AML、ALL中总体呈低表达趋势,PTEN在12例标本中有10例低表达,mTOR在12例标本中9例低表达,RICTOR在12例标本中7例低表达;FOXO1,CCND1在AML、ALL中则呈高表达趋势,FOXO1在12例标本中有9例高表达,CCND1在12例标本中7例高表达。结论:PI3K/AKT信号通路基因在白血病细胞中被激活。     

Retracted Article: Daphnetin inhibits proliferation and glycolysis in colorectal cancer cells by regulating the PI3K/Akt signaling pathway

Daphnetin (7,8-dihydroxycoumarin), a natural coumarin compound, has shown antitumor and energy metabolism regulatory activities. However, the effects of daphnetin on cell proliferation, migration, and glucose metabolism in colorectal cancer (CRC) cells remains unknown. In this study, the effects of daphnetin on CRC cell proliferation, migration, and glucose metabolism have been examined. The results showed that daphnetin inhibited the proliferation, migration, and invasion of CRC cells, and induced CRC cell apoptosis. Furthermore, daphnetin suppressed intracellular glucose and lactate production, and downregulated the expression of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) in CRC cells. Furthermore, daphnetin prevented activation of the PI3K/Akt pathway in CRC cells. These findings demonstrated that daphnetin inhibited the proliferation, migration and glucose metabolism in CRC cells by suppressing the PI3K/Akt signaling pathway. Therefore, daphnetin has potential as a novel anticancer agent for CRC treatment.

Daphnetin (7,8-dihydroxycoumarin), a natural coumarin compound, has shown antitumor and energy metabolism regulatory activities.     

Molecular targets for cancer therapy in the PI3K/AKT/mTOR pathway

Aberrations in various cellular signaling pathways are instrumental in regulating cellular metabolism, tumor development, growth, proliferation, metastasis and cytoskeletal reorganization. The fundamental cellular signaling cascade involved in these processes, the phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/AKT/mTOR), closely related to the mitogen-activated protein kinase (MAPK) pathway, is a crucial and intensively explored intracellular signaling pathway in tumorigenesis. Various activating mutations in oncogenes together with the inactivation of tumor suppressor genes are found in diverse malignancies across almost all members of the pathway. Substantial progress in uncovering PI3K/AKT/mTOR alterations and their roles in tumorigenesis has enabled the development of novel targeted molecules with potential for developing efficacious anticancer treatment. Two approved anticancer drugs, everolimus and temsirolimus, exemplify targeted inhibition of PI3K/AKT/mTOR in the clinic and many others are in preclinical development as well as being tested in early clinical trials for many different types of cancer. This review focuses on targeted PI3K/AKT/mTOR signaling from the perspective of novel molecular targets for cancer therapy found in key pathway members and their corresponding experimental therapeutic agents. Various aberrant prognostic and predictive biomarkers are also discussed and examples are given. Novel approaches to PI3K/AKT/mTOR pathway inhibition together with a better understanding of prognostic and predictive markers have the potential to significantly improve the future care of cancer patients in the current era of personalized cancer medicine.     

Long non-coding RNA CRNDE promote the progression of tongue squamous cell carcinoma through regulating the PI3K/AKT/mTOR signaling pathway

Long non-coding RNAs (lnRNAs) colorectal neoplasia differentially expressed (CRNDE) has been identified as a crucial regulator involved in tongue squamous cell carcinoma (TSCC). However, the molecular mechanism of CRNDE involved in TSCC progression is still unknown. In the study, qRT-PCR assay was used to detect the expression of CRNDE in TSCC tissues and cells. CCK-8 assay, colony formation assay, transwell assay and flow cytometric analysis were performed to determine cell proliferation ability, colony formation, migration and invasion capacities, and cell apoptosis, respectively. Western blot was employed to assess the activity of the PI3K/AKT/mTOR pathway. A xenograft mice model was performed to evaluate the role of CRNDE on tumor growth in vivo. The results showed CRNDE was upregulated in TSCC tissues and cell lines. CRNDE knockdown repressed the proliferation, colony formation, migration and invasion and promoted apoptosis in TSCC cells. Moreover, CRNDE regulated the PI3K/AKT/mTOR pathway in TSCC cells. Additionally, high levels of CRNDE inhibited tumor growth in vivo. In conclusion, high levels of CRNDE might promote TSCC progression at least partly through regulating the PI3K/AKT/mTOR pathway. Targeting CRNDE has potential to be used as a novel target of TSCC treatment.

Long non-coding RNAs (lnRNAs) colorectal neoplasia differentially expressed (CRNDE) has been identified as a crucial regulator involved in tongue squamous cell carcinoma (TSCC).     

Gab1在胃癌组织中表达分析及通过PI3K/AKT通路调控转移的机制研究

目的 探究Grb2相关结合蛋白1(Gab1)表达在胃癌中的临床意义和通过PI3K/AKT通路调控转移的机制.方法 收集2015年3月至2018年3月胃癌组织和癌旁组织标本各70份,通过免疫组织化学染色检测Gab1表达水平,并分析Gab1表达水平与患者一般资料和病理特点的相关性.将胃腺癌细胞AGS分为空白组、对照组、Ga...     

The m6A methyltransferase METTL14 inhibits the proliferation,migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway

Background N6‐methyladenosine (m6A) modification may participate in the regulation of occurrence and development of tumors. However, the m6A level and the potential regulatory mechanism of m6A in gastric cancer (GC) remain uncertain.MethodsRNA m6A quantification assay was conducted to detect the m6A level in GC tissues and cell lines. Methyltransferase‐like 14 (METTL14) expression in GC tissues was explored by bioinformatics and immunohistochemistry. Then, the function of METTL14 in GC cells was examined by CCK‐8, colony formation assay, wound healing assay, and Transwell assay. Besides, Western blotting was conducted to probe the PI3K/AKT/mTOR pathway and the epithelial‐mesenchymal transformation (EMT) pathway‐related gene expression.ResultsThe m6A modification level was decreased in GC and METTL14 was a key regulator resulting in m6A disorder in GC. METTL14 was downregulated in GC by analyzing both clinical samples and bioinformatics. METTL14 overexpression suppressed GC cell proliferation and aggression by deactivating the PI3K/AKT/mTOR pathway and the EMT pathway, respectively.ConclusionsOur findings indicate that METTL14 partakes in the biological process of GC as a tumor suppressor and may be an emerging biomarker in GC.     

Odontogenic ameloblast-associated protein (ODAM) inhibits human colorectal cancer growth by promoting PTEN elevation and inactivating PI3K/AKT signaling

Odontogenic ameloblast-associated protein (ODAM), an acidic matricellular protein, has been implicated in several epithelial neoplasms. However, its biological functions and molecular mechanisms in cancer progression, particular colorectal carcinoma (CRC), remain unknown. Here we demonstrated that ODAM was significantly down-regulated in CRC tissues compared with their normal counterparts. Then, we established that ODAM expression level was closely correlated with CRC development and patient prognosis. The abnormal expression of ODAM dramatically affected CRC cell growth in vitro and in vivo. We further revealed that the inhibitory effects of ODAM on CRC cell growth were associated with PTEN elevation and PI3K/AKT signaling inactivation. Furthermore, we determined that silencing of PTEN expression yielded recovery of AKT activity in ODAM-expressing CRC cells. Our study suggests matricellular protein ODAM may serve as a novel prognostic marker and act as a CRC growth suppressor.     

槲皮素通过PI3K/AKT/mTOR通路减轻脓毒症小鼠心肌损伤

目的基于磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)通路探究槲皮素减轻脓毒症小鼠心肌损伤的分子机制,为槲皮素治疗脓毒症提供理论依据。方法采用盲肠结扎穿孔法构建脓毒症小鼠模型,将造模成功的小鼠随机分为模型组、槲皮素组(200 mg/kg)、抑制剂组(PI3K/mTOR抑制剂NVP-BEZ235 60 mg/kg)和槲皮素+抑制剂组(槲皮素200 mg/kg+PI3K/mTOR抑制剂NVP-BEZ235 60 mg/kg),每组15只,另取15只小鼠作为假手术组。假手术组和模型组小鼠灌胃等体积生理盐水,其余各组灌胃相对应药物,给药体积10 m L/kg。给药24 h后,超声检测平均动脉压(MAP)、左心室收缩压(LVSP)、左心室等容舒张期压力下降最大速率(-dp/dtmax)和左心室等容舒张期压力上升最大速率(+dp/dtmax);全自动生化分析仪检测血清肌酸激酶同工酶(CK-MB)和心肌肌钙蛋白I(cTnI)水平;苏木素-伊红(HE)染色观察心肌组织病理学变化;酶联免疫吸附(ELISA)法检测心肌组织白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、丙二醛(MDA)和超氧化物歧化酶(SOD)含量;蛋白免疫印迹(Western blot)法检测心肌组织PI3K、AKT和mTOR蛋白磷酸化水平。结果心肌组织病理损伤:模型组小鼠心肌组织出现结构紊乱、心肌细胞变性、心肌纤维断裂、心肌横纹模糊、细胞间质水肿等病理损伤;槲皮素组较模型组减轻,抑制剂组较模型组加重;槲皮素+抑制剂组较槲皮素组加重。MAP、LVSP、-dp/dtmax、+dp/dtmax、SOD含量及PI3K、AKT、mTOR蛋白磷酸化水平:模型组较假手术组降低;槲皮素组较模型组升高,抑制剂组较模型组降低;槲皮素+抑制剂组较槲皮素组降低,较抑制剂组升高,差异均有统计学意义(P <0.05)。CK-MB、cTnI水平及TNF-α、IL-6、MDA含量:模型组较假手术组升高;槲皮素组较模型组降低,抑制剂组较模型组升高;槲皮素+抑制剂组较槲皮素组升高,较抑制剂组降低,差异均有统计学意义(P <0.05)。结论槲皮素可能通过上调PI3K/AKT/mTOR通路降低脓毒症小鼠心肌组织炎症和氧化应激反应,从而减轻心肌损伤。