肿瘤抑制基因PTEN研究新进展

PTEN是具有磷酸酶活性的抑癌基因,其低表达或缺失与肿瘤的进展及不良预后密切相关,其抑制肿瘤作用机制系通过抑制PI3K/AKT信号通路,FAK/PI30C和MAPK信号通路,FRAP/Mtor信号通路及影响核转录因子-Kb/IB信号通路;另外,NEDD4-1通过泛素化蛋白体降解途径调节PTEN,BMP通过RAS/ERK信号通路抑制PTEN表达,IGF-1通过IGF-1/PI3K/Akt信号通路调节PTEN.     

Ad-PTEN增强LY294002对人胶质瘤细胞系U251的生长抑制作用

目的在体外实验中,利用携带野生型PTEN基因的重组腺病毒（Ad—PTEN）和P13K的小分子抑制剂LY294002联合抑制P13K／AKT信号通路,观察两者联合对人胶质瘤细胞系U251生长有无正向协同作用及探讨产生这种作用的机制。方法15251细胞按处理方式不同分为4组：DMSO对照组、空载病毒对照组、LY294002组和联合组（LY294002＋Ad—PTEN组）。在U251细胞系中导入LY294002并转染Ad—PTEN病毒后,提取总蛋白,用Westernblotting检测PTEN表达状态及P13K、AKT表达情况;用MTT法检测Ad—PTEN和LY294002对U251生长抑制率、流式细胞仪检测细胞周期、AnnexinV法检测细胞凋亡,观察导人LY294002和转染Ad—PTEN后U251增殖能力的改变;用划痕实验、Transwell实验观察LY294002及Ad—PTEN对U251迁移和侵袭能力的影响;Westernblotting检测P13K／AKT信号通路下游相关蛋白表达水平变化。结果Westernblotting显示：与DMSO组和空载病毒组相比,LY294002组P13K、AKT蛋白表达水平明显降低,联合组（LY294002＋Ad—PTEN）的WEN蛋白明显上调,而P13K、AKT蛋白下降水平比LY294002组更为显著。联合组与LY294002组、空载病毒组、DMSO组相比细胞周期阻滞在G0／G1期;联合组凋亡率比其他三组明显增加;自培养第2天起,联合组细胞增殖速率呈下降趋势。联合组侵袭和迁移细胞的相对数少于LY294002组、空载病毒组和DMSO组。Westernblotting结果证明位于P13K／AKT下游的MMP-2、MMP-9、PCNA、Bcl-2、CyclinD1、NF—KB、FAK蛋白表达水平显著下调。结论小分子抑制剂LY294002能够有效抑制U251中P13K、AKT蛋白的表达,联合转染Ad—PTEN后不仅能提高PTEN蛋白的表达水平,对P13K、AKT的抑制更为显著。在体外实验中,联合Ad—PTEN和LY294002能够有效地通过阻滞细胞周期、减少细胞凋亡来抑制U251的增殖能力,并能够抑制细胞的侵袭和迁移能力,两者联合使用具有正向协同作用。联合Ad—PTEN和LY294002对U251的生长与侵袭的抑制作用与P13K／AKT下游的MMP-2、MMP-9、PCNA、Bcl-2、CyclinD1、NF—KB、FAK蛋白表达水平下调有关。联合腺病毒转染技术和小分子抑制剂调控P13K／AKT信号通路是治疗胶质瘤的新途径。     

BCR／ABL基因对PTEN介导的信号通路在K562细胞增殖和凋亡中的影响

目的：探讨BCR／ABL融合基因对抑癌基因PTEN介导的信号传导通路在K562细胞增殖和凋亡中的影响。方法：用不同浓度的格列卫（0．5、1、2、5、10μg／ml）干预K562细胞不同时间,观察其对细胞增殖的影响。用1μg／ml浓度的格列卫干预K562细胞不同时间（12、24、36、48、72h）后,通过荧光定量PCR检测细胞BCR／ABL、PTEN、mTOR mRNA水平的变化,并分析它们之间的相互关系。Western blotting检测细胞Akt和p-Akt水平,分析BCR／ABL融合基因对HEN mRNA表达的影响。结果：1μg／ml格列卫作用K562细胞后随着BCR／ABL融合基因表达减低,PTEN mRNA表达上调,mTOR mRNA表达下调,p-Akt表达下调。48h后随着BCR／ABL融合基因的抑制减弱,PTEN mRNA表达进而减低,而mTOR mRNA表达升高,p-Akt持续降低。BCR／ABL mRNA表达与PTEN mRNA表达呈负相关（r=-0．881,P〈0．05）,与mTOR mRNA及p-Akt表达呈正相关（依次为r=0．961,r=0．879,P均〈0．05）。结论：BCR／ABL融合基因可以通过抑制PTEN基因表达,调控P13K／Akt、mTOR信号传导通路,参与细胞增殖、凋亡及细胞周期调控等生物学特性。     

PDK／Akt通路与肿瘤治疗

磷酸肌醇-3激酶／蛋白激酶B（phosphoinositide 3-kinase／protein kinaseB，P13K／Akt）信号通路参与很多重要生物学过程的调控，但其过度激活可导致肿瘤的发生。在正常组织中P13K／Akt信号转导途径处于活化状态，但是该通路如果被过度激活则可通过下调肿瘤抑制蛋白p53、刺激蛋白质合成、抑制细胞凋亡等导致肿瘤细胞的无限增殖，成为肿瘤预后不好的标志，因此抑制该通路的激活有利于肿瘤治疗。目前已发现肿瘤抑制基因PTEN、PHLPP和蛋白磷酸酶2A等均可通过不同的机制抑制该通路的激活。同时，针对该通路的抑制剂作为抗肿瘤药物得到了广泛研究并在临床上取得了预期的进展，如wtPTEN的转基因研究、P13K抑制剂LY294002和渥曼青霉素、PDK-1抑制剂星孢菌素和塞来昔布、Akt抑制剂哌立福新、雷帕霉素靶蛋白（mTOR）抑制剂西罗莫司等，期望这些抑制剂能达到靶向治疗肿瘤的目的。     

PTEN-PI3K/AKT细胞信号转导通路与肿瘤

PTEN基因是近年来发现的一种新的肿瘤抑制基因,其产物PTEN蛋白具有脂质磷酸酶活性和蛋白磷酸酶活性。PI3K/AKT信号通路为生物体内重要的生存信号通路。实验证实PTEN主要是通过其脂质磷酸酶活性作用于PI3K的下游靶分子PIP3从而阻断PI3K/AKT信号通路来实现其抑癌作用,故有学者将它们称为PTEN-PI3K/AKT信号转导通路。本文中从细胞凋亡、细胞周期调节、细胞迁移与侵袭、血管形成、肿瘤耐药、肿瘤免疫逃逸等多个角度综述了PTEN-PI3K/AKT信号转导通路与肿瘤的关系。     

PTEN、P13K和mTOR在鼻咽癌中的表达及意义

目的：观察鼻咽癌（nasopharyngeal carcinoma,NPC）组织中PTEN、P13K和mTOR的表达,探讨其相互关系及其在鼻咽癌发生发展中的作用。方法：应用免疫组织化学方法检测PTEN、P13K和mTOR在60例鼻咽癌组织与23例鼻咽部慢性炎症组织中的表达水平。结果：60例NPC中,P13K表达的阳性率为86．7％（52／印）,mYOR为93．3％（56／60）,明显高于鼻咽部慢性炎症组60．9％（14／23）,69．6％（16／23）（P〈0．05）;60例NPC中,PTEN的表达率为41．7％（25／60）,明显低于鼻咽部慢性炎症组65．2％（15／23）（P〈0．01）;60例NPC中,PTEN的表达与mTOR、P13K的表达强度呈负（P〈0．05）,mTOR与P13K的表达强度呈正相关相关（P〈0．05）。结论：mTOR信号通路的激活与PTEN的抑制,可能在鼻咽癌的发生发展中起重要的作用。     

FTY720抑制裸鼠人肝癌细胞系MHCC-97H移植瘤生长的实验研究

目的 探讨不同浓度FTY720对裸鼠人肝癌MHCC-97H移植瘤的抑制作用。方法建立裸鼠肝脏的人肝癌细胞系MHCC-97H移植瘤模型,然后腹腔注射不同浓度的FTY720,治疗1个月后观察肿瘤的抑制效应,采用免疫组化法检测肿瘤细胞的增殖细胞水平。结果FTY720治疗组（5mg／kg和10mg／kg）能明显抑制肿瘤的生长,尤以10mg／kg更显著．FTY720治疗组的P13K—Akt信号通路被抑制,Caspase-3表达水平上调,提示FTY720明显促进肿瘤细胞凋亡。结论免疫抑制剂FTY720是1种有效抑制肝脏移植瘤的抗肿瘤分子,其可能与抑制P13K—Akt信号通路、上调Caspase-3表达水平,进而诱导细胞凋亡密切相关。     

PTEN/PI3K信号转导相关蛋白在非小细胞肺癌组织中的表达及其意义

背景与目的:PTEN/PI3K信号转导途径能调节细胞的增殖与存活,与多种肿瘤的发生发展密切相关,但在肺癌中所起的作用及其相互关系尚不十分明确。本研究旨在探讨PTEN/PI3K信号转导相关蛋白IGF-1R、PTEN和PI3K在非小细胞肺癌(non-smallcelllungcarcinoma,NSCLC)中的表达及其意义。方法:利用免疫组织化学SP法检测59例NSCLC组织、19例转移的淋巴结组织、16例癌旁增生肺组织和7例正常肺组织中IGF-1R、PTEN和PI3K蛋白的表达。IGF-1R、PTEN和PI3K蛋白阳性率的差异比较采用卡方检验和Fisher确切概率法。结果:59例NSCLC组织中IGF-1R、PTEN和PI3K蛋白阳性率分别为:72.88%、27.12%和84.75%。IGF-1R以及PI3K蛋白的阳性率与NSCLC的临床病理特征无显著相关(P>0.05)。PTEN蛋白的阳性率与NSCLC的组织学类型、细胞分化程度无关(P>0.05),但与淋巴结转移显著相关(P=0.009)。NSCLC组及转移淋巴结组中PI3K、PTEN蛋白的阳性率与正常肺组织和癌旁增生肺组织相比,差异均有显著性(P<0.05)。59例NSCLC组织中IGF和PI3K之间具有显著正相关性(P=0.001),Pearson列联系数为0.432。PTEN和PI3K之间具有显著负相关(P=0.000),Pearson列联系数为0.505。结论:IGF-1R、PI3K蛋白的过表达和PTEN蛋白的低表达与肺癌的发生及浸润转移相关。     

二苯乙烯苷抑制人乳腺癌MCF-7细胞增殖及对P13K／Akt信号通路的影响

目的：研究二苯乙烯苷（2,3,5,4’tetrahhydroxystilbene-2-O-β-D-glucoside,THSG）对体外培养的人乳腺癌MCF-7细胞增殖的作用及对P13K／Akt信号通路的影响。方法：M。rr法检测细胞增殖活性,AnnexinV／PI双标法检测细胞凋亡,Western印迹法检测PTEN、p-PKB、cvclinD1、Bcl-2、caspase3和NF-κB蛋白的表达,RT—PCR检坝4P13K上游抑制物PTENmRNA的表达。结果：1、10和100μmol／L的THSG处理细胞24、48和72h后,明显抑制MCF-7细胞增殖,100μmol／L作用48h的增殖抑制率为41．8％（P〈0．05）,但低浓度（0．1、0．01μmol／L）THSG出现弱的促增殖作用。1、10和100μmol／LTHSG作用48h后,MCF-7细胞凋亡率分别为（6．25&#177;0．65）％、（5．04&#177;0．83）％和（7．98&#177;0．67）％。1、10和100μmol／LTHSG上调PTEN的蛋白表达量,下调p-PKB和cyclinDI的蛋白表达,均呈剂量依赖性;而对NF-κB、Bcl-2和caspase-3表达却无明显影响。THSG能轻徽上调PTENmRNA水平。结论：THSG可抑制MCF-7细胞增殖,该作用可能是通过抑制P13K／Akt信号通路实现的。     

P13K／AKT／mTOR信号通路在乳腺癌Her-2治疗耐药中的作用研究进展

Her-2靶向治疗是Her-2过表达乳腺癌治疗的重要组成部分,但Her-2靶向治疗的耐药严重影响了乳腺癌的治疗。研究证实乳腺癌Her-2靶向治疗出现耐药的过程中有P13K／AKT／mTOR信号通路的激活,因此对P13K／AKT／mTOR信号通路及以P13K／AKT／mTOR信号通路为靶点的药物研究对乳腺癌治疗具有重要意义。     

PTEN’s regulation of VEGF and VEGFR1 expression and its clinical significance in myeloid leukemia

Phosphatase and tensin homolog (PTEN) acts as a novel tumor suppressor gene. PTEN protein plays an important role in regulating proliferation, apoptosis, invasion, and migration of many cancer cells. PTEN also modulates angiogenesis mediated by vascular endothelial growth factor (VEGF) via down-regulating PI3K/Akt pathway in many solid tumors. However, the effects of PTEN on VEGF and VEGFR1 (FLT1)-mediated angiogenesis, migration, invasion of leukemia cells, and its clinical significance are still unknown in myeloid leukemia. Therefore, we investigated the effect of PTEN on PI3K/Akt and VEGF/FLT1 pathways by transfecting wild-type PTEN gene to induce high expression of wild-type PTEN gene and protein in chronic myelogenous leukemia cell line K562 cells. We also observed the correlation between the expression levels of PTEN and VEGF/FLT1 and its clinical significance in myeloid leukemia patients. We found that the expression reconstitution of wild-type PTEN had significant effect on inhibiting proliferation, migration, and invasion abilities of K562 cells via down-regulation of Akt phosphorylation and inhibition of VEGF/FLT1 expression. In myeloid leukemia patients, a negative correlation was found between the expression level of PTEN mRNA and that of VEGF and FLT1 mRNA. Down-regulation of PTEN expression accompanied by up-regulation of VEGF and FLT1 mRNA indicated a higher tendency of extramedullary disease in acute myeloid leukemia patients. In conclusion, PTEN could modulate the function of VEGF/VEGFR signaling pathway down-regulation of Akt phosphorylation and that PTEN would be a candidate target to be addressed for inhibiting angiogenesis along with the treatment of myeloid leukemia.     

Loss of PTEN selectively desensitizes upstream IGF1 and insulin signaling

Many tumors have chronically elevated activity of PI 3-kinase-dependent signaling pathways, caused largely by oncogenic mutation of PI 3-kinase itself or loss of the opposing tumor suppressor lipid phosphatase, PTEN. Several PI 3-kinase-dependent feedback mechanisms have been identified that may affect the sensitivity of upstream receptor signaling, but the events required to initiate an inhibited state have not been addressed. We show that in a variety of cell types, loss of PTEN via experimental knockdown or in tumor cell lines correlates with a block in insulin-like growth factor 1 (IGF1)/insulin signaling, without affecting the sensitivity of platelet-derived growth factor or epidermal growth factor signaling. These effects on IGF/insulin signaling include a reduction of up to five- to tenfold in IGF-stimulated PI 3-kinase activation, a failure to activate the ERK kinases and, in some cells, reduced expression of insulin receptor substrate 1, and both IGF1 and insulin receptors. These data indicate that chronically elevated PI 3-kinase-dependent signaling to the degree seen in many tumors causes a selective loss of sensitivity in IGF1/insulin signaling that could significantly reduce the selective advantage of deregulated activation of IGF1/IGF1-R signaling in tumor development.     

miR-142-5p对人上皮性卵巢癌细胞增殖和凋亡的影响

目的:探讨miR-142-5p靶向PTEN-PI3K/Akt信号调控人上皮性卵巢癌SKOV3细胞增殖和凋亡的具体机制。方法:Real-time PCR检测miR-142-5p在人卵巢癌组织及各卵巢癌细胞系中的表达情况。利用MTT、细胞克隆形成实验观察miR-142-5p对SKOV3细胞增殖活力的影响;Caspase-3活力检测miR-142-5p对SKOV3细胞凋亡情况;信号通路抑制剂处理及Western blot检测miR-142-5p、PTEN与PI3K/Akt信号通路的关系及PI3K/Akt信号下游基因Akt、FOXO1、cyclin D1等的表达情况;Luciferase实验验证miR-142-5p和PTEN 3' UTR的结合。结果:人上皮性卵巢癌组织及其细胞系中miR-142-5p表达显著增加（P<0.05)。与对照组相比,SKOV3细胞转染miR-142-5p mimics后活细胞数量显著增加,增殖能力显著上升,细胞凋亡下降（P<0.05);与之相反的,转染miR-142-5p inhibitor后SKOV3细胞增殖能力下调,凋亡增加。信号通路抑制剂处理显示miR-142-5p过表达激活PI3K/Akt信号通路。Luciferase实验显示miR-142-5p与PTEN 3' UTR直接结合。与对照组相比,miR-142-5p mimics组PTEN表达显著降低,p-Akt蛋白表达则显著上调（P<0.05）,同时过表达PTEN后p-Akt表达则显著降低（P<0.05）。结论:miR-142-5p通过抑制PTEN基因表达活化PI3K/Akt信号通路,促进人上皮性卵巢癌组织及SKOV3细胞增殖存活,抑制细胞凋亡。     

SIRT1 promotes tumorigenesis of hepatocellular carcinoma through PI3K/PTEN/AKT signaling

SIRT1 is the human orthologue of SIR2, a conserved NAD-dependent protein deacetylase that regulates longevity in yeast and in Caenorhabditis elegans. Overexpression of SIRT1 in cancer tissue, compared with normal tissue, has been demonstrated, suggesting that SIRT1 may act as a tumor promoter. The function of SIRT1 in liver cancer has not been elucidated. In the present study, SIRT1 re-expression or knockdown was induced in hepatoma cell lines and liver normal cell lines. Our study demonstrated that overexpression of SIRT1 promoted mitotic entry of liver cells, cell growth and proliferation and inhibited apoptosis. The apoptosis involved caspase-3 and caspase-7, and was related to the PTEN/PI3K/AKT signaling pathway. The results demonstrate that SIRT1 promotes tumorigenesis of hepatocellular carcinoma (HCC) through the PTEN/PI3K/AKT signaling pathway. SIRT1 may serve as a novel target for selective killing of cancer versus normal liver cells.     

Effect of BRAF-mediated PI3K/Akt/mTOR pathway on biological characteristics and chemosensitivity of NSCLC A549/DDP cells

The present study aimed to explore the biological characteristics of non-small cell lung cancer (NSCLC) cells and the mechanism of chemosensitivity through the role of the PI3K/Akt/mTOR signaling pathway mediated by BRAF gene silencing. Following cell transfection and grouping, an MTT assay detected the activity of NSCLC cells, a scratch wound test assessed the migration ability, flow cytometry using PI staining detected the cell cycle phase, TUNEL and flow cytometry through Annexin V-PI staining assessed the apoptosis, and colony formation was used to detect the sensitivity of lung cancer cells to cisplatin chemotherapy. Furthermore, the relative expression levels of BRAF, PTEN, PI3K, mTOR mRNA were assessed by RT-qPCR, and the protein expression levels of BRAF, PTEN, PI3K, phosphorylated (p)-PI3K, Akt, p-Akt, mTOR, p-mTOR, cisplatin resistance-related enzymes ERCC1 and BRCA1, apoptotic proteins Bax and Bcl-2 were assessed by western blotting. Compared with the control group and NC group, there were differences in decreased BRAF mRNA expression levels in the small interfering (si)BRAF group and siBRAF + IGF-1 group (both P<0.05). In addition, compared with the control group, the siBRAF, NVP-BEZ235 and siBRAF + NVP-BEZ235 groups had significant decreased cell viability at 2–6 days, decreased migration ability, shortened proportion of S-phase cells, increased proportion of G₁/G₀-phase cells, increased apoptosis rate, decreased number of colony-forming cells, decreased mRNA expression of PI3K, Akt and mTOR, increased PTEN mRNA expression, decreased protein expression levels of PI3K, p-PI3K, Akt, p-Akt, mTOR, p-mTOR, ERCC1, BRCA1 and Bcl-2, and increased protein expression levels of PTEN and Bax (all P<0.05); and more obvious trends were revealed in the siBRAF + NVP-BEZ235 group (all P<0.05); whereas opposite results were detected in the siBRAF + IGF-1 group when compared with the siBRAF group and NVP-BEZ235 group (all P<0.05). Silencing of BRAF gene expression to inhibit the activation of the PI3K/Akt/mTOR signaling pathway exerted a synergistic effect decreasing cell viability, inhibiting the cell cycle and migration, increasing the apoptosis rate, decreasing the number of colony-forming cells and increasing chemosensitivity of NSCLC. Activation of the PI3K/Akt/mTOR signaling pathway may reverse the role of silencing of BRAF gene expression, providing a potential approach for improving the chemosensitivity of NSCLC. The present study for the first time, to the best of our knowledge, clarified the possible mechanism of NSCLC cell biological characteristic changes and chemosensitivity from the perspective of BRAF gene silencing and PI3K/Akt/mTOR signaling pathway activation, providing a potential reference for suppressing tumor aggravation and improving the therapeutic outcomes of NSCLC at the genetic level.     

PI3K inhibitors in trastuzumab-resistant HER2-positive breast cancer cells with PI3K pathway alterations

The activation of the PI3K signaling pathway resulting from genetic alterations induces carcinogenesis and resistance to anticancer therapies. Breast cancer is a major malignancy that is associated with dysregulation of the PI3K signaling pathway. PIK3CA mutations and PTEN loss occur in every subtype of breast cancer. PI3K inhibitors are being evaluated in breast cancer after the success of an alpha isoform-specific PI3K inhibitor in estrogen receptor (ER)-positive/HER2-negative metastatic breast cancer. Some preclinical data indicate the potential for PI3K/mTOR targeting in combination with trastuzumab for HER2-positive breast cancer with or without expression of the estrogen receptor. However, the role of this therapy in HER2-positive breast cancer with PIK3CA mutations and/or PTEN loss remains unclear. We examined three HER2-positive, ER-negative breast cancer cell lines to determine the efficacy of a novel alpha isoform-specific PI3K inhibitor in combination with trastuzumab. The results indicated that this combination was effective in PIK3CA-mutant or PTEN-deficient breast cancer cells by inducing apoptosis and inhibiting the expression of downstream proteins. PTEN loss by siRNA modulation in parental HER2-positive cancer cells with PI3K signaling pathway alterations could not confer resistance to alpelisib or GDC-0077 plus trastuzumab. We selected the CK-MB-1 cell line without alterations in the PI3K pathway to demonstrate that PI3K inhibitors plus trastuzumab represented a biomarker-specific treatment. In vivo effects of alpelisib plus trastuzumab were tested and confirmed in a mouse model, showing the combination strategy offered the best opportunity to achieve tumor volume reduction. With known safety profiles, this cytotoxic chemotherapy-free regimen warrants further attention as a biomarker-driven strategy for treating HER2-positive breast cancer.     

Reduced PTEN expression in breast cancer cells confers susceptibility to inhibitors of the PI3 kinase/Akt pathway.

The PTEN protein is a lipid phosphatase with putative tumor suppressing abilities, including inhibition of the PI3K/Akt signaling pathway. Inactivating mutations or deletions of the PTEN gene, which result in hyper-activation of the PI3K/Akt signaling pathway, are increasingly being reported in human malignancies, including breast cancer, and have been related to features of poor prognosis and resistance to chemotherapy and hormone therapy. Prior studies in different tumor models have shown that, under conditions of PTEN deficiency, the PI3K/Akt signaling pathway becomes a fundamental proliferative and survival pathway, and that pharmacological inhibition of this pathway results in tumor growth inhibition. This study aimed to explore further this hypothesis in breast cancer cells. To this end, we have determined the growth response to inhibition of the PI3K/Akt signaling pathway in a series of breast cancer cell lines with different PTEN levels. The PTEN-negative cell line displayed greater sensitivity to the growth inhibitory effects of the PI3K inhibitor, LY294002 and rapamycin, an inhibitor of the PI3K/Akt downstream mediator mTOR, compared with the PTEN-positive cell lines. To determine whether or not these differences in response are specifically due to effects of PTEN, we developed a series of cell lines with reduced PTEN protein expression compared with the parental cell line. These reduced PTEN cells demonstrated an increased sensitivity to the anti-proliferative effects induced by LY294002 and rapamycin compared with the parental cells, which corresponded to alterations in cell cycle response. These findings indicate that inhibitors of mTOR, some of which are already in clinical development (CCI-779, an ester of rapamycin), have the potential to be effective in the treatment of breast cancer patients with PTEN-negative tumors and should be evaluated in this setting.     

EYA1 通过调控PTEN/PI3K/AKT信号通路抑制胃癌SGC-7901 细胞的恶性生物学行为

[摘要] 目的:探讨EYA1(eyes absent 1)通过调控PTEN/PI3K/AKT信号通路抑制胃癌SGC-7901细胞的恶性进展及其相关机制。方法:收集2016年6月至2018年6月陆军军医大学附属西南医院全军普通外科中心29例胃癌组织及其癌旁组织标本,采用Wb和qPCR实验检测胃癌组织和癌旁组织中EYA1 mRNA和蛋白的表达水平。人胃癌细胞株SGC-7901培养完成后,采用过表达EYA1质粒或siRNA干扰质粒转染胃癌SGC-7901细胞;分别采用MTT、流式细胞术、划痕愈合和Transwell实验检测胃癌SGC-7901细胞的增殖、凋亡、迁移和侵袭能力。结果:胃癌组织中EYA1 mRNA 和蛋白表达水平较癌旁组织均明显降低（P<0.01）;过表达EYA1可明显提高SGC-7901 细胞的增殖、迁移和侵袭能力（均P<0.05）、抑制细胞凋亡（P<0.05）。过表达EYA1 可明显促进PTEN的表达、抑制PI3K/AKT通路的激活（均P<0.05或P<0.01）;但在PTEN干扰后以上作用均受到了明显抑制（均P<0.05或P<0.01）。结论:EYA1可通过促进PTEN的表达抑制PI3K/AKT信号通路,从而抑制胃癌SGC-7901细胞的恶性生物学行为。