共查询到20条相似文献,搜索用时 15 毫秒
1.
目的:探讨槲皮苷是否通过抑制PI3K/AKT信号通路诱导人胃癌SGC7901细胞凋亡。方法:选取SGC7901细胞作为研究对象,采用MTT法检测槲皮苷对SGC7901细胞的毒性作用并测定IC50值。实验分为对照组(不加药处理)、槲皮苷组(采用200μmol/L槲皮苷处理)、PI3K/AKT通路激动剂胰岛素样生长因子1(IGF-1)组(采用100μg/L IGF-1处理)和槲皮苷+IGF-1组(采用200μmol/L槲皮苷+100μg/L IGF-1共处理)。处理48 h后,采用流式细胞术检测细胞凋亡,Western blot法检测cleaved caspase-3、p-AKT(Ser473)、AKT、p-PI3K(Tyr508)和PI3K的蛋白水平。结果:从100μmol/L开始,随着槲皮苷处理浓度的逐渐升高,SGC7901细胞活力显著降低(P 0. 05),槲皮苷作用48 h的IC50值为275. 40μmol/L。200μmol/L槲皮苷作用SGC7901细胞48 h后,与对照组比较,细胞凋亡率和cleaved caspase-3蛋白水平显著上升(P 0. 05),p-AKT和p-PI3K蛋白水平显著降低(P 0. 05),然而IGF-1与槲皮苷共同作用时,IGF-1可逆转槲皮苷对SGC7901细胞的作用效果。结论:槲皮苷能够诱导胃癌SGC7901细胞凋亡,其作用机制可能与抑制PI3K/AKT信号通路的激活有关。 相似文献
2.
目的:探究乌骨藤提取物(Marsdenia tenacissima extract,MTE)对黑色素瘤细胞活力及凋亡的作用及机制。方法:用不同浓度(0、50、100和200 mg/L) MTE处理小鼠皮肤黑色素瘤B16-F10细胞24 h或不同浓度MTE处理不同时间(0、24、48、72和96 h),MTT法检测细胞活力。流式细胞术检测细胞凋亡情况,Western blot法检测细胞增殖、凋亡和PI3K/AKT/mTOR通路相关蛋白的表达,同时检测通路激动剂胰岛素样生长因子1(IGF-1)处理细胞后p-PI3K及细胞增殖和凋亡相关蛋白的表达。结果:根据预实验结果,选择MTE作用时间为72 h。MTE浓度为100 mg/L和200 mg/L时能明显抑制B16-F10细胞活力及增殖相关蛋白Ki67和PCNA的表达,并且还可诱导B16-F10细胞凋亡,提高凋亡相关蛋白cleaved caspase-3和cleaved caspase-9的蛋白水平;同时,MTE还可显著降低p-PI3K、p-AKT和mTOR的蛋白水平;此外,激动剂IGF-1可明显减弱MTE抑制细胞活力及诱导细胞凋亡的作用。结论:MTE可通过下调PI3K/AKT/mTOR通路活性抑制黑色素瘤细胞活力,诱导细胞凋亡。 相似文献
3.
目的:探讨毒蕈碱胆碱受体3(muscarinic receptor 3,M3R)激动剂卡巴胆碱促进人肺癌A549细胞上皮间质转化的可能信号通路。方法:用400μmol/L卡巴胆碱刺激人肺癌A549细胞,在倒置相差显微镜下观察细胞形态的变化,应用划痕愈合实验和Transwell实验观察细胞迁移和侵袭能力;应用q PCR技术检测上皮间质转化相关蛋白波形蛋白(vimentin)和E钙黏蛋白(E-cadherin)m RNA水平的变化;应用Western blot技术检测p-AKT、vimentin和E-cadherin蛋白水平的变化。结果:卡巴胆碱刺激人肺癌A549细胞后,细胞形态发生明显改变,由不规则多边形逐渐向梭形转化、细胞间紧密结合逐渐变得松散,细胞迁移和侵袭能力增强;vimentin的m RNA和蛋白表达量明显增加,E-cadherin的m RNA和蛋白水平降低,磷酸化的AKT蛋白水平增加,且这些变化均可被M3R特异性抑制剂4-DAMP所抑制(P0.05)。结论:卡巴胆碱可通过激活PI3K/AKT信号途径促进人肺癌A549细胞发生上皮间质转化。 相似文献
4.
Kun Xie Jianze Nian Xingyang Zhu Xiaoping Geng Fubao Liu 《International journal of clinical and experimental pathology》2015,8(11):14028-14033
Increasing evidences have indicated the role of garlicin in inhibiting the progression of various tumors including glioma, pulmonary carcinoma and pancreatic carcinoma, via mediating cell apoptosis or cell cycle. The regulatory effect and related molecular mechanism of garlicin in intrahepatic cholangiocarcinoma, however, remained unknown. This study thus aimed to investigate this scientific issue. HCCC-9810 cell line was treated with serially diluted garlicin, followed by cell proliferation assay using MTT approach. Transwell migration and invasion assays were further employed the regulatory effect of garlicin. The expression level of p-AKT and AKT proteins in tumor cells was quantified by Western blot. The growth of tumor cells was significantly inhibited by high concentration of garlicin (> 1.5 μM). Lower concentration of garlicin showed dose-dependent inhibition of tumor cell invasion and migration. After using specific agonist IGF-1 (50 ng/mL) of PI3K/AKT signaling pathway, such facilitating effects of garlicin were depressed (P < 0.05). Western blotting showed significantly decreased phosphorylation level of AKT after treated with gradient concentrations of garlicin, while leaving the total AKT protein level unchanged. Garlicin may inhibit the invasion and migration of intrahepatic cholangiocarcinoma cells via inhibiting PI3K/AKT signaling pathway. 相似文献
5.
目的:探讨参慈胶囊联合顺铂是否通过PI3K/AKT/mTOR信号通路逆转接种人肺腺癌A549/DDP细胞的裸鼠体内的顺铂耐药。方法:建立裸鼠人肺腺癌移植瘤模型,随机分为对照组、参慈胶囊组、顺铂组和参慈胶囊+顺铂组。对照组予生理盐水,其余各组荷瘤裸鼠均用药21 d,断颈处死,取肿瘤组织,采用流式细胞术检测细胞周期与细胞凋亡;采用FQ-PCR技术检测A549/DDP肺癌组织PTEN、P-糖蛋白、PI3K、AKT和mTOR的mRNA表达情况。结果:参慈胶囊组、顺铂组和参慈胶囊+顺铂组与对照组比较,对人肺腺癌A549/DDP细胞的增殖均有抑制作用,其中参慈胶囊+顺铂组较其它治疗组能够进一步将人肺腺癌A549/DDP细胞阻滞于G_2/M期,促进细胞凋亡,增加PTEN的表达,抑制P-糖蛋白、PI3K、AKT和mTOR的表达。结论:参慈胶囊可能通过阻断PI3K/AKT/mTOR信号通路,促进PTEN的表达,或者抑制P-糖蛋白介导的耐药途径,增强裸鼠体内人肺腺癌A549/DDP耐药细胞对顺铂的敏感性。 相似文献
6.
Yan Zhang Shi-Jie Wang Zhen-Hua Han Yong-Qin Li Jia-Hong Xue Deng-Feng Gao Xiao-San Wu Cong-Xia Wang 《International journal of clinical and experimental pathology》2014,7(11):8112-8117
The aim of this study was to investigate the effect of PI3K/AKT signaling pathway in the activity of recombinant human angiotensin converting enzyme 2 (rhACE2) promoted the activity of endothelial nitric oxide synthase (eNOS). The human umbilical vein endothelial cells (HUVEC) were cultured in vitro. Then treated with Ang II (1×10-6 mol/L) for 24 h. The rhACE2 (100 μmol/L) was added and incubated for 5, 10, 15, 30, 60 min respectively which was based on Ang II intervention. The effect of rhACE2 on phosphorylation eNOS level was also observed in the presence of (10 μmol/L) (PI3K/AKT inhibitors). Griess reagent method was applied to measure NO contents in cell culture supernatant, RT-PCR to detect the expression of eNOSmRNA in HUVEC, and Western blot to detect the expression of eNOS and phosphorylated eNOS. In Ang II intervention group, NO contents were significantly lower than control group (P < 0.05). Through rhACE2 treatment, the NO contents in cell culture medium and the expression level of phosphorylated eNOS were significantly higher than in Ang II intervention group (P < 0.05), but eNOSmRNA and non-phosphorylated eNOS protein expression level showed no significant difference (P > 0.05). After HUVEC was intervened by PI3K/AKT pathway inhibitor LY294002, the expression level of phosphorylated eNOS was significantly lower than that in the rhACE2 30 min treatment group (P < 0.05). rhACE2 may reduce the activity of Ang II inhibited endothelial cell eNOS, which can be blocked by PI3K/AKT pathway inhibitor LY294002, suggesting PI3K/AKT signaling pathway plays an important role in rhACE2’s promotion of the activity of endothelial cell eNOS. LY294002相似文献
7.
Lei-Lei Yang Peng-Fei Zhang Tian-Yu Zhang Wei Shen Yong Zhao Shen Yin 《Environmental and molecular mutagenesis》2019,60(9):830-836
Ortho-phenylphenol (OPP), as an active ingredient of disinfectants, has been worldwide utilized as fungicides and antibacterial agents in hospital, agriculture, wood preservation, and veterinary products. However, little is known about the toxic effects of OPP on male reproduction, especially sperm motility, and the underlying mechanisms. In this study, we chose porcine sperms as in vitro model to investigate the effects and mechanisms of OPP exposure on sperm motility. Our results indicated that porcine sperm motility decreases significantly in a dose-dependent manner after exposed to OPP. Additionally, ATP synthesis deficiency was revealed by downregulation of ATP synthase subunit beta and adenosine 5′-monophosphate-activated protein kinase expression. Furthermore, OPP disturbed the expression of TP53 and PTEN, which contributed to AKT pathway deactivation. OPP exposure also disrupted platelet-derived growth factor receptor A expression, which further inhibited 3-phosphoinositide-dependent protein kinase 1 activation, resulting in protein kinase B and pyruvate dehydrogenase phosphatase catalytic subunit 1 deactivation. In conclusion, these observations suggest that OPP exposure decreases porcine sperm motility by disturbing the AMPK/AKT signaling pathway. Environ. Mol. Mutagen. 2019. © 2019 Wiley Periodicals, Inc. 相似文献
8.
《Human immunology》2021,82(12):960-967
ObjectiveTo explore the effect of LINC00323 on the polarization of M1 macrophages in diabetic nephropathy. To study the effect and biological mechanism of LINC00323 on the occurrence and development of diabetic nephropathy.MethodsWe used clinical samples to analyze the correlation between macrophage polarization and the occurrence and development of diabetic nephropathy. In addition, we used bioinformatics to analyze the key molecules of macrophage polarization. We then verified the key pathways that promote the M1 polarization of macrophages at the level of cell biology. And we verify the effectiveness of treatment against this target in animal experiments.ResultsWe analyzed in clinical samples that the expression of inflammatory factors (TNF-α and IL-6) increased in patients with diabetic nephropathy. In addition, we found that the expression of M1 marker protein CD86 increased through PCR and western blot analysis. We found a key target (LINC00323) through bioinformatics. The expression of LINC00323 in patients' blood samples is also at a high level. We further explored the mechanism of LINC00323 involved in the polarization of M1 macrophages at the level of cellular molecular biology, and found that it is closely related to the PI3K/AKT signaling pathway. In animal models, we found that inhibiting the expression of LINC00323 can reduce the damage of diabetic nephropathy.ConclusionWe found that LINC00323 mediates the polarization of M1 macrophages through the PI3K/AKT signaling pathway. LINC00323 plays an important role in the occurrence and development of diabetic nephropathy. 相似文献
9.
《Pathology, research and practice》2020,216(9):153087
Methyltransferase-like 3 (METTL3) is identified as a methyltransferase responsible for N6-methyladenosine (m6A) modification of mRNA, miRNA and lncRNA. Emerging evidences suggest that METTL3 is involved in tumorigenesis and progression of multiple tumor types. However, the functional role of METTL3 in esophageal cancer (EC) remains unclear. We used specific shRNA to down-regulate the METTL3 expression, and used pcDNA3.1-METTL3 cDNA plasmid to up-regulate the METTL3 expression in Eca-109 and KY-SE150 cells. Biological functions of METTL3 were performed by CCK-8, colony formation, apoptosis analysis, transwell and wound healing assays. Finally, an in-depth mechanism study was performed by an AKT inhibitor. METTL3 knockdown reduced the proliferation, clonality, migration and invasion of Eca-109 and KY-SE150 cells, and induced cell apoptosis, which may be mediated by activation of the mitochondrial apoptotic pathway. Further, METTL3 overexpression promoted the proliferation, clonality, migration and invasion of Eca-109 and KY-SE150 cells, and inhibited cell apoptosis. In addition, METTL3 regulated the expression of Wnt/β-catenin and AKT signaling pathway components. A double-effect inhibitor (BEZ235) inhibited AKT and mTOR phosphorylation and hindered the effect of METTL3 overexpression on the proliferation and migration of Eca-109 and KY-SE150 cells. Our data suggest that METTL3 plays a carcinogenic role in human EC progression partially through AKT signaling pathways, suggesting that METTL3 may serve as a potential therapeutic target for EC therapy. 相似文献
10.
Sartelet H Imbriglio T Nyalendo C Haddad E Annabi B Duval M Fetni R Victor K Alexendrov L Sinnett D Fabre M Vassal G 《Histopathology》2012,60(7):1144-1155
Sartelet H, Imbriglio T, Nyalendo C, Haddad E, Annabi B, Duval M, Fetni R, Victor K, Alexendrov L, Sinnett D, Fabre M & Vassal G (2012) Histopathology 60, 1144–1155 CD133 expression is associated with poor outcome in neuroblastoma via chemoresistance mediated by the AKT pathway Aims: Neuroblastoma is a frequent childhood cancer with a heterogeneous prognosis. CD133 expression is an independent prognostic marker for a low survival rate in several cancers. The aim of this study was to determine the prognostic value of CD133 expression in a large cohort of neuroblastoma cases, to define the chemoresistance of neuroblastoma cells expressing CD133, and to determine whether this chemoresistance is regulated by activation of the AKT pathway. Methods and results: Two hundred and eighty samples of neuroblastoma were screened for CD133 expression. The sensitivity of purified CD133+ neuroblastoma cells isolated from two human cell lines to doxorubicin, vincristine and cisplatin, as single agents or in combination with LY294002, an AKT inhibitor, was evaluated in vitro. CD133 expression was found in 100 of 280 tumours. There was a significant association between CD133 expression and the following poor prognosis covariates: age, International Neuroblastoma Staging System stage, MYCN amplification, and phospho‐AKT (pAKT) expression. Patients with CD133? tumours had significantly better 3‐year event‐free and overall survival than patients with CD133+ tumours. In a multivariate model, CD133 expression was independently associated with decreased overall survival. CD133high neuroblastoma cells were significantly resistant to chemotherapy as compared with CD133low cells. Treatment of unsorted neuroblastoma cells with the three anticancer drugs significantly enriched the CD133+ subpopulation. CD133high cells expressed significantly higher levels of pAKT than CD133low cells. LY294002 treatment abolished the preferential survival of CD133high cells. Conclusions: CD133 is associated with in‐vitro resistance to chemotherapy involving activation of the AKT pathway. 相似文献
11.
Yi-Jin Li Bao-Kang Dong Meng Fan Wen-Xue Jiang 《International journal of clinical and experimental pathology》2015,8(10):12410-12418
B cell translocation gene 2 (BTG2) has been reported to be a potential tumor suppressor in many types of tumors. However, the roles and molecular mechanisms of BTG2 in osteosarcoma progression are still unknown. In this study, we investigated the role of BTG2 in proliferation and metastasis of osteosarcoma and the underlying mechanism. BTG2 expression levels were measured in fresh osteosarcoma tissues and cell lines. The effects of BTG2 on cell proliferation, migration and invasion were explored by MTT, transwell assays, western blot, and in vivo tumorigenesis in nude mice. We found that BTG2 was down-regulated in human osteosarcoma tissues and cell lines. Overexpression of BTG2 inhibited the proliferation and migration/invasion of human osteosarcoma cells in vitro, it also markedly inhibited xenograft tumor growth in vivo. Furthermore, BTG2 significantly decreased the expression of phosphorylated PI3K and AKT in osteosarcoma cells. Taken together, our data indicate that BTG2 might suppress the tumor growth and metastasis via PI3K/AKT signaling pathway, implying that BTG2 may serve as a potential molecular target for the treatment of osteosarcoma. 相似文献
12.
目的:研究DEK表达下调对胃癌SGC-7901细胞凋亡的影响,并分析其与NF-κB信号途径及凋亡相关蛋白表达的关系。方法:将DEK siRNA和对照siRNA转染胃癌SGC-7901细胞,并将SGC-7901细胞分为未处理组、对照siRNA组及DEK siRNA组。采用实时荧光定量PCR和Western blot检测3组胃癌SGC-7901细胞中DEK mRNA和蛋白的表达;流式细胞术检测3组SGC-7901细胞凋亡的变化;Caspase-Glo-3/9试剂盒检测3组SGC-7901细胞中caspase-3和caspase-9的活性;Western blot技术检测3组SGC-7901细胞中NF-κB信号途径关键调控蛋白p65及凋亡相关蛋白Bcl-2和Bax的表达。结果:与未处理组和对照siRNA组相比,DEK siRNA组SGC-7901细胞中DEK的mRNA和蛋白表达水平显著下调(P0.05)。DEK siRNA组SGC-7901细胞的早期凋亡率和总凋亡率均显著高于未处理组和对照siRNA组(P0.05)。最为显著的是,DEK siRNA转染细胞后,p65和Bcl-2蛋白表达下调,Bax蛋白表达上调,并伴随caspase-3和caspase-9活性上升。结论:DEK表达下调介导的SGC-7901细胞凋亡可能与NF-κB信号途径密切相关。 相似文献
13.
目的:探讨瓜蒌皮提取物(FTPE)对高脂饮食诱导的肥胖小鼠脂肪组织慢性炎症的影响及作用机制.方法:雄性C57BL/6J小鼠随机选取10只为对照组,其余小鼠喂养高脂饲料建立肥胖模型,造模成功后分为模型组、PI3K抑制剂(LY294002,7.5 mg/kg)组、低剂量(2 mL/kg)FTPE(FTPE-L)组、高剂量(... 相似文献
14.
《Pathology, research and practice》2019,215(12):152641
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. 相似文献
15.
目的:探讨钙敏感受体(calcium-sensing receptor,CaSR)在缺氧诱导的A549及A549/DDP细胞增殖中的信号转导途径。方法:通过缺氧培养箱内(93%N_2、2%O_2、5%CO_2)培养24 h的方法复制细胞缺氧模型。应用Western blot技术分析PCNA及p-AKT蛋白不同处理情况下的表达水平;采用流式细胞技术检测不同处理因素对细胞周期及增殖指数的影响,应用BrdU掺入法分析不同处理因素对细胞DNA合成的影响。结果:缺氧引起A549及A549/DDP细胞PCNA及p-AKT蛋白水平上调,增加BrdU掺入量、S期细胞数量和细胞增殖指数,GdCl_3能够增强缺氧的作用,但上述效应可以被LY294002抑制。结论:PI3K/AKT信号通路在缺氧活化CaSR并促进A549及A549/DDP细胞增殖中起重要作用。 相似文献
16.
目的 探讨周期性张应变对人牙周膜细胞 (human periodontal ligament cell , hPDLCs ) 增殖的影响及其相关机制。方法 应用FX-4000T 细胞应变加载系统,对体外培养的人牙周膜细胞施加周期性张应变,幅度分别为10 % 和20 %,加载时间为6 h和24 h,频率均为0.1 Hz,以未加载的静态细胞作为对照组。Western blot 法检测细胞增殖细胞核抗原(PCNA)和细胞内信号转导分子p-ERK1/2表达的变化。用ERK1/2的特异性抑制剂PD 98059预处理细胞后,在0.1 Hz,10 % 幅度条件下,加载6 h,检测p-ERK1/2的表达水平变化对细胞PCNA表达的影响。 结果 与静态组相比,周期性张应变诱导人牙周膜细胞的PCNA和p-ERK1/2表达增加,10 % 幅度和20 % 幅度相比无显著性差异。同一幅度张应变,加载6 h和24 h对细胞PCNA和p-ERK1/2表达的影响无显著性差异。ERK1/2的抑制剂PD98059不仅可以明显抑制张应变诱导的p-ERK1/2 活化,而且张应变诱导的细胞PCNA表达也被明显抑制。结论 周期性张应变可激活ERK信号通路,促进体外培养人牙周膜细胞的增殖。 相似文献
17.
目的:探讨白藜芦醇抗小鼠炎性痛的核因子κB(nuclear factor-κB,NF-κB)信号通路机制。方法:将60只BALB/c小鼠随机分为正常对照组、炎性痛模型组、阳性对照(地塞米松,0.5 mg/kg)组及白藜芦醇(100、50和25 mg/kg)组,每组10只。通过测定小鼠机械刺激缩足反射阈值、热刺激缩足反应潜伏期及冷缩足反射次数,观察白藜芦醇是否具有缓解小鼠炎性痛的作用。采用RT-PCR和Western blot法检测炎性痛小鼠脊髓组织(L4~L6)NF-κB、NF-κB抑制蛋白α(inhibitor of NF-κBα,IκBα)、NF-κB抑制蛋白激酶β(inhibitor of NF-κB kinaseβ,IKKβ)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)及白细胞介素1β(interleukin-1β,IL-1β)的mRNA和蛋白表达水平的影响。结果:白藜芦醇(100和50 mg/kg)可明显升高完全弗氏佐剂(complete Freund’s adjuvant,CFA)所致炎性痛小鼠机械刺激缩足反射阈值,显著延长其热刺激缩足反应潜伏期,减少其冷缩足反射次数(P0.05或P0.01);白藜芦醇(100 mg/kg)可明显下调CFA诱导的炎性痛小鼠脊髓组织NF-κB、IκBα、IKKβ、TNF-α及IL-1β的mRNA和蛋白表达水平(P0.05或P0.01)。结论:白藜芦醇对炎性痛具有较好的缓解作用,其机制可能与抑制NF-κB信号通路有关。 相似文献
18.
目的:探究丹参酮ⅡA对人骨肉瘤HOS细胞增殖和凋亡的影响及机制。方法:采用CCK-8实验考察丹参酮ⅡA对HOS细胞活力的影响,并确定给药剂量。集落形成实验与细胞迁移实验研究丹参酮ⅡA对肿瘤细胞增殖与迁移能力的影响。Hoechst 33258染色、透射电镜与流式细胞技术检测丹参酮ⅡA对肿瘤细胞凋亡的影响。Western blot进一步检测细胞凋亡与JNK通路相关蛋白的变化;并通过JNK抑制剂验证肿瘤细胞中上述通路与凋亡的关系。结果:一定剂量的丹参酮ⅡA能抑制HOS细胞的增殖与迁移能力,且效应呈浓度依赖与作用时间依赖性,并能诱导凋亡发生。Western blot进一步表明,随着药物浓度增加,cleaved caspase-3与Bax蛋白水平上升,Bcl-2蛋白表达下降,JNK通路相关蛋白表达上升,这些变化可被JNK抑制剂SP600125缓解。CCK-8实验结果显示,抑制JNK通路可减少药物导致的细胞活力抑制。结论:丹参酮ⅡA可通过JNK通路诱导人骨肉瘤HOS细胞发生凋亡,具有显著抑制肿瘤细胞增殖的作用。 相似文献
19.
Jingzhe Yang Chengli Wang Zhijie Zhang Xiaojun Chen Yusen Jia Bin Wang Tao Kong 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2017,125(2):134-140
Prostate cancer is one of the most common malignancies in men, and it urgently demands precise interventions that target the signaling pathways implicated in its initiation, progression, and metastasis. The Notch‐1 signaling pathway is closely associated with the pathophysiology of prostate cancer. This study investigated the antitumor effects and mechanisms of curcumin, which is a well‐known natural compound from curcuminoids, in prostate cancer cells. Viability, proliferation, and migration were analyzed in two prostate cancer cell lines, DU145 and PC3, after curcumin treatment. Whether the Notch‐1 signaling pathway is involved in the antitumor effects of curcumin was examined. Curcumin inhibited the survival and proliferation of PC3 and DU145 cells in a dose‐ and time‐dependent manner and inhibited DU145 migration. Curcumin did not affect the expression of Notch‐1 or its active product NICD, but it did inhibit the expression of MT1‐MMP and MMP2 proteins in DU145 cells. We found that curcumin inhibited the DNA‐binding ability of NICD in DU145 cells. In conclusion, curcumin inhibited the survival and metastasis of prostate cancer cells via the Notch‐1 signaling pathway. 相似文献
20.
Juanpere N Agell L Lorenzo M de Muga S López-Vilaró L Murillo R Mojal S Serrano S Lorente JA Lloreta J Hernández S 《Human pathology》2012,43(10):1573-1582
Different members of the phosphoinositide 3 kinase - serine threonine protein kinase (PI3K-AKT) pathway are altered in bladder cancer. Fibroblast growth factor receptor 3 (FGFR3) mutations characterize the low-grade tumors, and RAS genes are mutated in approximately 13% of all bladder tumors. Interestingly, a percentage of bladder tumors have alterations in more than 1 PI3K-AKT or rat sarcoma viral oncogene homolog-RAF mitogen activated protein kinase (RAS-MAPK) pathway gene or their upstream regulators, but some combinations are mutually exclusive. We analyzed mutations in FGFR3, phosphoinositide 3 kinase catalytic alpha polypeptide (PIK3CA), v-akt murine thymoma viral oncogene homolog 1 (AKT1), v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS), and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) in 88 urothelial cell carcinomas and the immunohistochemical expression of phospho-v-akt murine thymoma viral oncogene homolog (AKT) and mitogen-activated protein kinase 1 and 2 (pERK1/2) in 80 and 77 urothelial cell carcinomas, respectively. Approximately 43% and 20.5% of tumors presented 1 and 2 mutated genes, respectively. FGFR3 mutations were more frequent alone, whereas PIK3CA mutations were associated with another mutated gene (FGFR3 and KRAS). Overall, mutated FGFR3 (FGFR3(mut)) and mutated FGFR3 (FGFR3(mut))-mutated PIK3CA (PIK3CA(mut)) genotypes were associated with low-grade bladder tumors and mutated PIK3CA (PIK3CA(mut))-mutated KRAS (KRAS(mut)) and mutated AKT1 (AKT1(mut)) were only present in high-grade tumors. There are no mutated FGFR3 (FGFR3(mut))-mutated RAS (RAS(mut)) nor mutated PIK3CA (PIK3CA(mut))-mutated AKT1 (AKT1(mut)) combinations. Fifty percent and 56% of tumors showed high levels of pAKT and pERK1/2, respectively. High levels of pAKT were associated with total mutations, FGFR3(mut), and PIK3CA(mut) tumors but not with tumor grade or stage. Wild-type tumors presented significantly higher pERK1/2 expression. Mutations in FGFR3 and FGFR3-PIK3CA but not single PIK3CA mutations characterize low-grade bladder tumors. Single FGFR3 or PIK3CA mutations and the different mutation combinations FGFR3-PIK3CA/AKT1 and PIK3CA-RAS can activate the AKT but not the MAPK pathway. Other genes different from FGFR3 may be related with the pERK activation in bladder tumors. 相似文献