Knockdown of Aurora-B inhibits osteosarcoma cell invasion and migration via modulating PI3K/Akt/NF-κB signaling pathway

Increasing evidences reveal that Aurora-B may be involved in metastasis of malignant tumor. In this study, we investigated the inhibitory effect of Aurora-B on invasion and migration of OS cells and the activity of PI3K/Akt/NF-κB signaling pathway in vitro. The expression of Aurora-B and p-Akt (Ser473) proteins was detected by immunohistochemistry in OS tissues from 24 patients with pulmonary metastatic disease, and the relationship between Aurora-B and p-Akt was investigated. The results showed that there was a positive correlation between Aurora-B and p-Akt protein expression. Furthermore, we down-regulated the expression of Aurora-B through a recombinant lentivirus (Lv-shAURKB). Migration and invasion of cells were investigated by wound healing and transwell invasion assays. Results showed that silencing Aurora-B inhibited cell migratory and invasive ability of OS cells in vitro. Finally, knockdown of Aurora-B suppresses the activity of PI3K/Akt/NF-κB signaling pathway in OS cells. Our results indicated that knockdown of Aurora-B suppresses OS cells migratory and invasive ability via modulating the “PI3K/Akt/NF-κB” signaling pathway in vitro. The Aurora-B blocker may be a new therapeutic strategy in OS management.     

慢病毒短发夹RNA介导的多形性腺瘤基因样蛋白2沉默对肝癌细胞MHCC97-L增殖、迁移及侵袭的影响

目的 探讨慢病毒短发夹RNA(shRNA)介导的多形性腺瘤基因样蛋白2(PLAGL2)沉默对肝癌细胞恶性行为的影响及其机制.方法 Real-time PCR与Western blotting分别检测肝癌组织及癌旁组织中PLAGL2的表达水平;体外培养肝癌细胞MHCC97-L,构建慢病毒载体质粒PLAGL2-shRNA与...     

Knockdown of PFTK1 inhibits tumor cell proliferation,invasion and epithelial-to-mesenchymal transition in pancreatic cancer

PFTK1 was identified as a member of the cyclin-dependent kinase (CDK) family and it is frequently upregulated in many types of tumors. However, its expression and role in pancreatic cancer has not been yet reported. In this study, we aimed to explore the expression and function in pancreatic cancer. The present study verified that PFTK1 was highly expressed in pancreatic cancer cell lines. The in vitro experiments demonstrated that knockdown of PFTK1 inhibited the proliferation, migration and invasion of pancreatic cancer cells as well as the epithelial-to-mesenchymal transition (EMT) progress. Finally, knockdown of PFTK1 inhibited the expression of p-PI3K and p-Akt in pancreatic cancer cells. In summary, the present study has provided further evidence that knockdown of PFTK1 inhibited the proliferation and invasion of pancreatic cancer cells as well as the EMT progress by suppressing the PI3K/Akt signaling pathway. Therefore, these findings reveal that PFTK1 might potentially become a novel strategy for targeting pancreatic cancer.     

CTHRC1 facilitates bladder cancer cell proliferation and invasion through regulating the PI3K/Akt signaling pathway

IntroductionEmerging evidence has illustrated that Collagen triple helix repeat containing 1 (CTHRC1) is crucial for tumorigenesis and development. However, the effects of CTHRC1 on bladder cancer progression remain largely unclear. Here, we aim to investigate the function and mechanism of CTHRC1 in behaviors of bladder cancer cells in vitro and in vivo.Material and methodsInterference assays were applied to determine the biological functions of CTHRC1. The expression of CTHRC1 was examined by quantitative real time-PCR (qRT-PCR), Western blot and immunohistochemical (IHC) analysis. Effects of CTHRC1 on proliferation, migration and invasion were evaluated by CCK-8, colony formation, flow cytometry, EdU staining, wound healing, transwell and western blot assays. Bladder cancer cells transfected with sh-CTHRC1 were injected into nude mice to explore the effect of CTHRC1 on tumorigenesis in vivo.ResultsCTHRC1 expression was increased in bladder cancer tissues and cell lines compared with normal controls, and associated with advanced clinical stage and lymph node metastasis. Also, patients with high levels of CTHRC1 expression were found to have a poor prognosis. Knockdown of CTHRC1 alleviated bladder cancer cell proliferation, migration and invasion in vitro and impeded tumorigenesis in vivo. Moreover, mechanistic investigation indicated that CTHRC1 could regulate the PI3K/Akt signaling pathway.ConclusionsOur data demonstrated that CTHRC1 played an oncogenic role in bladder cancer by modulating the PI3K/Akt signaling pathway, which sheds novel light on diagnosis and treatment of bladder cancer.     

Lidocaine inhibits the proliferation and invasion of hepatocellular carcinoma by downregulating USP14 induced PI3K/Akt pathway

Previous studies have found that Lidocaine (Lido) has marked anti-tumor effects. The purpose of this study was to explore the effect and mechanism of Lido on hepatocellular carcinoma (HCC). Here, the Huh-7 and SMMC-7721 HCC cells were treated with Lido, then the proliferation, migration and invasion of HCC cells were detected by CCK8, wounding healing assay and Transwell assay. Besides, apoptotic proteins (including Caspase3 and Bcl2), epithelial-mesenchymal transition (EMT) associated markers (including E-cadherin and Vimentin), USP14, PI3K/Akt pathway were detected by western blot. Our results revealed that Lido significantly inhibited the proliferation, migration and invasion while aggravate the apoptosis of HCC cells, as well as the expression of USP14 and the activation of PI3K/Akt. Loss-of-function experiments confirmed that USP14 downregulation attenuated the malignant behaviors of HCC cells through repressing PI3K/Akt signaling pathway. Mechanistically, USP14 functioned by deubiquitinating and activating PI3K. In conclusion, Lido inhibits the proliferation and metastasis of HCC cells by targeting USP14 and its downstream PI3K/Akt signaling pathway.     

下调晚期糖基化终末产物受体对乳腺癌细胞 增殖、凋亡、侵袭、迁移能力的影响*

目的：研究下调晚期糖基化终末产物受体（RAGE）对乳腺癌细胞增殖、凋亡、侵袭、迁移能力的影响。 方法：培养乳腺癌BT474 细胞,分为对照组（ 不做任何处理的乳腺癌BT474 细胞）、上调组（ 乳腺癌BT474 细 胞+RAGE阴性对照）、下调组（ 乳腺癌BT474 细胞+RAGE siRNA）。用四甲基偶氮唑盐法检测乳腺癌细胞增 殖、凋亡水平;用Transwell 法检测乳腺癌细胞迁移、侵袭水平;用免疫印迹法检测细胞PI3K/Akt 信号通路蛋白 PI3K、p-PI3K、Akt、p-Akt、caspase 3、Bcl-2、Bax 表达量。结果：下调组细胞不同时间点增殖率均显著低于 上调组、对照组。下调组细胞不同时间点凋亡率均显著高于上调组、对照组。下调组细胞迁移、侵袭数均显著 低于上调组、对照组。下调组p-PI3K、PI3K、Akt、p-Akt、Bcl-2 蛋白表达量低于上调组、对照组,caspase 3、 Bax 蛋白表达量高于上调组、对照组。结论：经下调RAGE作用于PI3K/Akt 信号通路,其可抑制p-PI3K、PI3K、 Akt、p-Akt、Bcl-2 表达,促进caspase 3、Bax 表达,致乳腺癌细胞凋亡,抑制乳腺癌细胞增殖、侵袭、迁移。     

MEX3A通过PI3K/Akt信号通路促进结直肠癌细胞的增殖和迁移

目的 探讨MEX3A在结直肠癌(CRC)中的表达水平,及MEX3A对结直肠癌细胞增殖和迁移的影响及作用机制.方法 通过TCGA数据库获取327例数据(正常组织41例,肿瘤组织286例),收集临床样本104例(癌旁组织27例,癌组织77例),进行免疫组织化学染色,分析MEX3A在结直肠癌和正常组织间表达的差异.利用Wes...     

MicroRNA-133b inhibits proliferation and invasion of ovarian cancer cells through Akt and Erk1/2 inactivation by targeting epidermal growth factor receptor

Aberrant expression of microRNA-133b (miR-133b) has been frequently reported in some cancers excluding ovarian cancer (OC). The role and its molecular mechanism of miR-133b in OC have not been reported. In this study, we explored the effects of miR-133b overexpression on proliferation and invasion in OC cells. The mRNA level of miR-133b in OC cell lines was determined by real-time PCR. The miR-133b mimic was transiently transfected into OC cells using Lipofectamine™ 2000 reagent. Subsequently, cell proliferation and invasion were assessed by MTT, Brdu-ELISA and Transwell assays. Moreover, the effects of miR-133b overexpression on the MAPK and PI3K/Akt signaling pathways were determined by Western blot. Protein level of EGFR was also measured by Western blotting. Meanwhile, luciferase assays were performed to validate EGFR as miR-133b target in OC cells. Our results showed that the mRNA level of miR-133b was remarkably decreased in OC cell lines compared with normal colon epithelium cells, whereas the protein expression of EGFR was significantly increased. Up-regulation of miR-133b inhibited the proliferation and invasion of OC cells. We also found that miR-133b overexpression evidently decreased the phosphorylation of Erk1/2 and Akt. Bioinformatics analysis predicted that the EGFR was a potential target gene of miR-133b. Luciferase reporter assay demonstrated that miR-133b could directly target EGFR. Altogether, our results indicated that miR-133b overexpression was shown to inhibit proliferation and invasion of OC cells through suppression of the MAPK and PI3K/Akt signaling pathways by targeting EGFR.     

DDX3表达上调在人宫颈癌细胞增殖中的作用分析

目的:探讨DDX3表达上调在人宫颈癌细胞增殖中的作用。方法:采用免疫组织化学方法检测2012年4月至2013年3月河南省人民医院59例宫颈癌组织及癌旁非肿瘤组织标本中的DDX3表达情况。同时,以宫颈癌细胞HeLa为研究对象,通过慢病毒介导的宫颈癌细胞过度表达来检测DDX3的功能。采用细胞增殖与活性检测试剂盒评估细胞存活...     

DNM3OS Facilitates Ovarian Cancer Progression by Regulating miR-193a-3p/MAP3K3 Axis

PurposeLong non-coding RNAs (lncRNAs) are essential regulators in the development of ovarian cancer (OC). Nonetheless, the function of lncRNA DNM3 opposite strand/antisense RNA (DNM3OS) in OC remains unclear. This work aimed to investigate the biological roles and underlying mechanisms of DNM3OS in OC.Materials and MethodsQuantitative real-time polymerase chain reaction was conducted to examine DNM3OS, microRNA (miR)-193a-3p, and mitogen-activated protein kinase 3 (MAP3K3) mRNA expression in OC tissues and cell lines. Kaplan-Meier survival analysis was employed to analyze the relationship between DNM3OS expression and the prognosis of OC patients. Cell counting kit-8, 5-ethynyl-2′-deoxyuridine, and transwell experiments were conducted to monitor cell proliferation, migration, and invasion, respectively. Western blot was applied to examine epithelial-mesenchymal transition associated protein (E-cadherin and N-cadherin) expression. Luciferase reporter gene and RNA immunoprecipitation experiments were performed to confirm the relationships among DNM3OS, miR-193a-3p, and MAP3K3. Pearson''s correlation analysis was adopted to analyze the correlations among DNM3OS, miR-193a-3p, and MAP3K3 mRNA.ResultsDNM3OS expression was remarkably increased in OC tissues and cell lines, which was associated with the unfavorable prognosis of the patients. DNM3OS overexpression enhanced OC cell proliferation, migration, and invasion; suppressed E-cadherin protein expression; and facilitated N-cadherin protein expression, while the transfection of miR-193a-3p mimics had the opposite effects. DNM3OS directly interacted with miR-193a-3p, and miR-193a-3p targeted MAP3K3 by directly binding to 3′UTR. DNM3OS could up-regulate the expression of MAP3K3 via repressing miR-193a-3p expression.ConclusionDNM3OS, as an oncogenic lncRNA, increases the malignancy of OC cells via regulation of an miR-193a-3p/MAP3K3 axis.     

黏蛋白16基因通过磷酸肌醇3-激酶/蛋白激酶B通路调节胆囊癌细胞活力和迁移

目的 探讨黏蛋白16基因（MUC16）是否通过磷酸肌醇3-激酶/蛋白激酶B（PI3K/Akt）通路调节胆囊癌细胞（GBC-SD）活力和迁移。 方法 过表达MUC16后,通过Real-time PCR筛选相关基质金属蛋白酶（MMP）家族的蛋白质。其次,过表达MUC16、敲低MUC16和PI3K/Akt通路抑制剂BKM120处理后,通过免疫印迹法检测PI3K/Akt通路和MMP-9的蛋白水平。最后,过表达MUC16或敲低MUC16,通过细胞计数试剂盒8（CCK-8）和刮伤实验检测GBC-SD的活力和迁移情况。 结果 过表达MUC16后,MMP-9 mRNA的相对表达量显著升高（P<0.05）。过表达MUC16后, MMP-9、p-Akt、PI3K的蛋白水平明显升高（P<0.05）,但是PI3K抑制剂BKM120可以避免这现象。而敲低MUC16后,发现MMP-9、p-Akt、PI3K的蛋白水平明显降低（P<0.05）。过表达MUC16后,GBC-SD的细胞活力和迁移能力明显增高（P<0.05）,而敲低了MUC16后,GBC-SD的细胞活力和迁移能力明显降低（P<0.05）。另外,敲低MMP-9后,GBC-SD的细胞活力和迁移能力也明显降低（P<0.05）。但是,在过表达MUC16的同时敲低MMP-9,发现GBC-SD的细胞活力和迁移能力与对照组相比差异无显著性（P>0.05）。 结论 MUC16激活PI3K/Akt通路促进MMP-9的蛋白表达,进而提升胆囊癌细胞GBC-SD的细胞活力和迁移能力。     

羽扇豆醇增强对沉默ST3GalⅢ基因的MDA-MB-231细胞侵袭转移的抑制作用

目的 探索羽扇豆醇（Lupeol）增强对沉默ST3GalⅢ基因的人乳腺癌MDA-MB-231细胞侵袭转移的抑制作用。方法 体外培养沉默ST3GalⅢ基因的MDA-MB-231细胞。采用细胞黏附实验,Transwell侵袭实验,细胞划痕实验检测羽扇豆醇对ST3GalⅢ沉默的MDA-MB-231细胞侵袭转移能力的作用。Western blotting检测各组细胞转移相关基质金属蛋白酶（MMP）-2、9和磷脂酰肌醇-3激酶/蛋白激酶B/核因子κB（PI3K/Akt/NF-κB）信号通路蛋白的表达情况。结果 ST3GalⅢ基因沉默及低浓度（5 μmol/L）羽扇豆醇对MDA-MB-231细胞的增殖及凋亡无明显影响。羽扇豆醇对ST3GalⅢ沉默的MDA-MB-231细胞黏附、迁移和侵袭有明显的抑制作用,且相关蛋白MMP-2、-9和PI3K/Akt/NF-κB信号通路蛋白表达均下调。结论 羽扇豆醇体外能增强对沉默ST3GalⅢ基因的人乳腺癌MDA-MB-231细胞侵袭和转移的抑制作用,其机制可能与抑制MMP-2、-9的蛋白表达及影响了PI3K/Akt/NF-κB信号通路有关。     

调控FOXM1基因对乳腺癌BT474细胞赫赛汀药物敏感性的影响

目的探究调控叉头框转录因子M1(FOXM1)基因对乳腺癌BT474细胞赫赛汀药物敏感性的影响。方法将FOXM1过表达及特异性靶向FOXM1基因的小干扰RNA(FOXM1-siRNA)转染至乳腺癌BT474细胞,将细胞分为上调FOXM1基因组、下调FOXM1基因组和对照组。Western blot检测FOXM1蛋白以及PI3K/AKT信号通路蛋白的表达。MTT法检测不同浓度赫赛汀药物对BT474细胞增殖能力的影响。Transwell实验检测不同浓度赫赛汀药物对BT474细胞迁移、侵袭能力的影响。结果下调FOXM1基因后,FOXM1蛋白的相对表达量明显减少(P<0.05)。上调FOXM1基因组BT474细胞的增殖率、迁移数量、侵袭数量显著高于对照组,且随着赫赛汀浓度的增加其增殖率、迁移数量、侵袭数量逐渐增加,上调FOXM1基因可增强BT474细胞对赫赛汀的耐药性,促进增殖、迁移及侵袭。下调FOXM1基因组BT474细胞的增殖率、迁移数量、侵袭数量显著低于对照组,低浓度的赫赛汀对BT474细胞的增殖、迁移及侵袭能力的抑制程度较弱,高浓度的赫赛汀对BT474细胞的增殖、迁移及侵袭能力的抑制过度,而中浓度的赫赛汀抑制能力介于低、高浓度之间,能够有效抑制BT474细胞增殖、迁移及侵袭,但无抑制过度的表现。不同赫赛汀浓度下下调FOXM1基因组细胞的增殖率、迁移数量、侵袭数量显著低于上调FOXM1基因组。下调FOXM1基因组PI3K、p-PI3K、AKT、p-AKT蛋白相对表达量均低于对照组和上调FOXM1基因组(P<0.05)。结论上调FOXM1基因可增强乳腺癌BT474细胞对赫赛汀的耐药性,下调FOXM1基因在中浓度赫赛汀的干预下,可通过作用于PI3K/AKT信号通路,抑制乳腺癌BT474细胞的增殖、迁移及侵袭,从而抑制乳腺癌的发展。     

Tumor-associated macrophages promote the metastasis of ovarian carcinoma cells by enhancing CXCL16/CXCR6 expression

This study investigated the underlying mechanism by which C-X-C motif chemokine ligand 16 (CXCL16)/C-X-C motif chemokine receptor 6 (CXCR6) signaling is activated by tumor-associated macrophages and assists in regulating the metastasis of ovarian carcinoma. Specimens of ovarian carcinoma tissue and adjacent tissue were collected from 20 ovarian carcinoma patients. Human THP-1 cells were induced to differentiate into macrophages, which were then co-cultured with SKOV3 cells and low concentrations of tumor necrosis factor-α (TNF-α) to simulate the inflammatory microenvironment of ovarian carcinoma. Additionally, small interfering RNA (siRNA) targeting CXCR6 was transfected into SKOV3 cells; after which, the levels of nuclear factor kappa B p65 (NF-κB p65) protein and phosphorylated PI3K and Akt were measured. The migration and invasion abilities of the SKOV3 cells were also tested. The levels of TNF-α, interluekin-6 (IL-6), NF-κB p65, CXCL16, and CXCR6 expression in the ovarian carcinoma tissues were higher than those in the precancerous tissues. CXCR6 expression was positively correlated with TNF-α, IL-6, and CXCL16 expression. Co-culture of SKOV3 cells with macrophages significantly promoted CXCL16, CXCR6, NF-κB, and p65 expression by the SKOV3 cells, increased their levels of phosphorylated PI3K and Akt, and increased the migration and invasion abilities of SKOV3 cells. Silencing of CXCR6 or blocking the PI3K/Akt signal pathway markedly attenuated the expression of NF-κB p65 and phosphorylation of PI3K and Akt, as well as the migration and invasion abilities of SKOV3 cells. These findings demonstrate that macrophages can promote the migration and invasion of ovarian carcinoma cells by affecting the CXCL16/CXCR6 pathway.     

RETRACTED: Long noncoding RNA TUG1 facilitates cell ovarian cancer progression through targeting MiR-29b-3p/MDM2 axis

Ovarian cancer (OC) is one of the most aggressive female cancers in the world. OC trends to be diagnosed at an advanced stage with abdominal metastasis. Our study explored the biological function and underlying mechanism of lncRNA on OC cell proliferation and migration. The expression of turine up-regulated gene 1 (TUG1) in human OC tissues and cell lines was measured by qRT-PCR. OC cell proliferation, viability, migration, and invasion were measured by MTT assays, colony formation assays, and transwell assays in vitro. Furthermore, the nude mice xenograft model was established to determine the effects of TUG1 in vivo. The relationship between TUG1 and miR-29b-3p, as well as miR-29b-3p and MDM2 were identified using the luciferase reporter assays. We showed that the expression of TUG1 and MDM2 were significantly increased, but the expression of miR-29b-3p was remarkably decreased in OC tissues and cell lines. Knockdown of TUG1 strongly inhibited the ability of cell proliferation, colony formation, migration, and invasion in vitro. The relationship between TUG1 and miR-29b-3p, or miR-29b-3p and MDM2 were predicted by StarBase and miRanda online software. Besides, miR-29b-3p reversed the positive effect of TUG1 on the OC cell proliferation, migration, and invasion through inhibiting MDM2 expression and increasing p53 phosphorylation level. Moreover, knockdown of TUG1 suppressed tumor growth in vivo. Taken all together, this study shows that TUG1 plays a crucial oncogenic role and facilitates cell proliferation, migration, and invasion in OC through regulating miR-29b-3p/MDM2 axis.     

CNTN-1 promotes docetaxel resistance and epithelial-to-mesenchymal transition via the PI3K/Akt signaling pathway in prostate cancer

IntroductionTherapy options for prostate cancer (PCa) typically are centered on docetaxel-based chemotherapy but are limited by the effects of multi-drug resistance. Recent advances have illustrated a role of contactin-1 (CNTN-1) in tumor chemoresistance, while the function and mechanism of CNTN-1 in the resistance of docetaxel in prostate cancer have not yet been elucidated.Material and methodsDocetaxel (Dox)-resistant PCa cell lines of PC3 (PC3-DR) and DU145 (DU145-DR) were established, and short hairpin RNA (shRNA) constructs targeting CNTN-1 were generated to analyze the effect of knockdown of CNTN-1 on PCa progression. Cell Counting Kit-8 (CCK-8), flow cytometry, wound-healing, transwell and western blotting analysis were used to analyze cell proliferation, apoptosis, migration, invasion and related protein expression levels, respectively.ResultsKnockdown of CNTN-1 in PC3-DR and DU145-DR cells attenuated cell proliferation, migration, invasion, EMT phenotype, and drug resistance, and increased cell apoptosis further reduced the tumorigenic phenotype. Knockdown of CNTN-1 resulted in an anti-tumor effect in the xenograft tumor model, and decreased activity of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway both in vitro and in vivo.ConclusionsThe results of the present study suggest that downregulation of CNTN-1 may be an important mechanism to reverse chemoresistance in Dox-resistant PCa progression, thus shedding light on the development of novel anti-tumor therapeutics for the treatment of PCa.     

Desmocollin 3 mediates follicle stimulating hormone-induced ovarian epithelial cancer cell proliferation by activating the EGFR/Akt signaling pathway

Follicle-stimulating hormone (FSH) is associated with the pathogenesis of ovarian cancer. We sought to explore whether desmocollin 3 (Dsc3) mediates FSH-induced ovarian epithelial cancer cell proliferation and whether the EGFR/Akt signaling pathway may be involved in this process. Dsc3 positivity in ovarian tissue specimens from 72 patients was assessed by immunohistochemistry. The positive expression rates of Dsc3 were similar in ovarian cancer tissues (24/31:77.4%) and borderline ovarian tumor tissues (18/22:81.8%) (P>0.05), but were significantly higher in these cancerous tissues than in benign ovarian cyst tissues (3/19:15.8%) (P<0.05). Consistently, the expression of Dsc3 in four out of five ovarian cancer cells (HO8910, Skov3ip, Skov and Hey cells, but not ES-2 and in borderline ovarian MCV152 tumor cells was higher than in the immortalized ovarian epithelial cell line, Moody. FSH up-regulated the expression of Dsc3 and EGFR in a dose- and time-dependent manner. Furthermore, a converse relationship between the expression of Dsc3, EFGR and PI3K/Akt signaling was elucidated using RNA interference and PI3K/Akt inhibitor in the absence and presence of FSH. A role for these proteins in FSH-induced cell proliferation was verified, highlighting their interdependence in mediating ovarian cancer cell function. These results suggest that Dsc3 can mediate FSH-induced ovarian cancer cell proliferation by activating the EGFR/Akt signaling pathway.     

MicroRNA-129-5p suppresses proliferation,migration and invasion of retinoblastoma cells through PI3K/AKT signaling pathway by targeting PAX6

BackgroundRetinoblastoma (RB) is the most common primary intraocular malignancy in children. Accumulating evidences have clarified that microRNAs (miRNAs) modulated signaling molecules by acting as oncogenes or tumor-suppressor genes in RB. Thus, in our study, we aimed to investigate the function of miR-129-5p in RB cells through PI3K/AKT signaling pathway by targeting PAX6. Two RB cell lines, Y79 and WERI-Rb-1, were selected in our study, followed by transfection of miR-129-5p inhibitor or si-PAX6 to explore the regulatory role of miR-129-5p in RB cell proliferation, invasion and migration.Material and methodsDual-luciferase assay was used for the detection of targeting relationship between miR-129-5p and PAX6. Besides, western blot analysis was applied to detect expression of cell cycle-related factors (CDK2 and Cyclin E) and PI3K/AKT signaling pathway-related factors (p-AKT and AKT). Nude mice tumorigenesis experiment was used to evaluate the effect of miR-129a-5p on RB growth in vivo.ResultsmiR-129-5p was down-regulated in RB cell lines. miR-129-5p directly targeted the 3′-untranslated region of PAX6. Artificial down-regulation of miR-129-5p promoted cell proliferation, migration and invasion in RB cell lines Y79 and WERI-Rb-1, and promoted RB growth in vivo via PI3K/AKT signaling pathway, which could be reversed by transfection with silencing PAX6.ConclusionThis study provides evidences that RB progression was suppressed by overexpressed miR-129-5p via direct targeting of PAX6 through PI3K/AKT signaling pathway, which may provide a molecular basis for better treatment for RB.     

丙泊酚对人胶质瘤U251细胞株增殖、凋亡、侵袭和转移能力的调节作用

目的　探究丙泊酚对人胶质瘤U251细胞增殖、凋亡、侵袭和转移能力的作用和机制。 方法 将细胞随机分为U251组、Propofol（1 mM）组、Propofol（2 mM）组和Propofol（5 mM）组。除U251组外,其余组用相应浓度的丙泊酚处理,CCK8检测细胞增殖,流式检测细胞凋亡,Transwell检测细胞侵袭能力,划痕实验检测细胞迁移能力,Western blot检测Ki67、Caspase-3、血管内皮生长因子（Vascular endothelial growth factor, VEGF）、磷脂酰肌醇-3-羟激酶（Phosphoinositide 3-kinase, PI3K）、Akt、p-PI3K和p-Akt的表达。 结果 与U251组比较,Propofol （1, 2, 5 mM）组细胞增殖速度明显降低,细胞凋亡率显著升高;同时,Propofol （1, 2, 5 mM） 组侵袭细胞数与U251组比较明显减少,Propofol（2, 5 mM） 组划痕闭合率明显低于U251组;此外,丙泊酚还能显著抑制细胞增殖和迁移相关蛋白Ki67和VEGF表达,诱导细胞凋亡相关蛋白Caspase-3表达;丙泊酚能明显降低p-PI3K/PI3K和p-Akt/Akt的比值。 结论 丙泊酚能降低胶质瘤U251细胞的增殖、侵袭和转移能力,抑制U251细胞凋亡,作用机制可能与抑制PI3K/Akt信号通路激活有关。     

Ginkgol C17:1 inhibits tumor growth by blunting the EGF-PI3K/Akt signaling pathway

Ginkgol C17:1 has been shown to inhibit apoptosis and migration of cancer cells, but the underlying mechanisms are not fully elucidated. In this study, we explored whether the inhibitory effects of Ginkgol C17:1 were associated with epidermal growth factor receptor (EGFR) and PI3K/Akt signaling. The results showed that EGF treatment increased the phosphorylation of EGFR, PI3K, Akt, mTOR and NF-kB, and also enhanced the proliferation, migration and invasion of HepG2 cells. Ginkgol C17:1 dose-dependently inhibited EGF-induced phosphorylation/activation of all the key components including EGFR, PI3K, Akt, mTOR and NF-kB, leading to a significant reduction either of proliferation or migration and invasion of HepG2 cells. Notably, treatment with Ginkgol C17:1 in mice suppressed the growth of tumor mass in vivo, and expression of EGFR in the tumor tissue. The results suggest that Ginkgol C17:1 is a potent tumor inhibiting compound that acts on EGF-induced signal transduction of the PI3K/vjjhhAkt signaling pathways, and may represent a clinically interesting candidate for cancer therapy.