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1.
Colon cancer (CC) is the third most common cancer worldwide. Emodin is an anthraquinone-active substance that has the ability to affect tumor progression. Our study aims to explore the effects and the relevant
mechanism of emodin on the invasion and migration of CC in vitro and in vivo. In our study, we found that
emodin inhibited the invasion and migration abilities of RKO cells and decreased the expression of matrix
metalloproteinase-7 (MMP-7), MMP-9, and vascular endothelial growth factor (VEGF) in a dose-dependent
manner. Further research suggested that emodin inhibited EMT by increasing the mRNA level of E-cadherin
and decreasing the expression of N-cadherin, Snail, and b-catenin. Emodin also significantly inhibited the
activation of the Wnt/b-catenin signaling pathway by downregulating the expression of related downstream
target genes, including TCF4, cyclin D1, and c-Myc. A Wnt/b-catenin signaling pathway agonist abolished
the effect of emodin on EMT and cell mobility, suggesting that emodin exerted its regulating role through the
Wnt/b-catenin pathway. The CC xenograft model was established to study the antitumor efficiency of emodin
in vivo. The in vivo study further demonstrated that emodin (40 mg/kg) suppressed tumor growth by inhibiting EMT via the Wnt/b-catenin signaling pathway in vivo. Taken together, we suggest that emodin inhibits the
invasion and migration of CC cells in vitro and in vivo by blocking EMT, which is related with the inhibition
of the Wnt/b-catenin signaling pathway. 相似文献
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大黄素、芹菜素抑制人卵巢癌细胞侵袭的体外实验研究 总被引:24,自引:2,他引:22
背景与目的:大黄素抑制酪氨酸蛋白激酶、酪蛋白激酶2的活性,抑制I-κB降解;芹菜素抑制丝裂原活化蛋白激酶、PI3K的活性。大黄素、芹菜素是否能抑制高恶性度肿瘤侵袭与转移的研究还未见报道,本研究选用大黄素、芹菜素,观察其对人卵巢癌细胞体外侵袭的作用。方法:台盼蓝活细胞拒染法观察药物对人卵巢癌细胞生长、增殖的影响;以人工重组基底膜(Matrigel)体外侵袭实验观察药物对细胞体外侵袭、粘附、运动能力的影响;SDS-聚丙烯酰胺凝胶电泳法观察对Ⅳ型胶原酶分泌及活性的影响。结果:大黄素及芹菜素均抑制HO-8910PM细胞的生长、增殖,其48h的IC50分别为(35.30±3.50)μmol/L和(28.92±2.60)μmol/L。大黄素有效抑制HO-8910PM细胞体外侵袭、粘附、运动,在40μmol/L时,抑制率分别为(45.31±3.10)%、(25.42±1.70)%和(41.59±1.90)%;大黄素抑制基质金属蛋白酶-9(MMP-9)分泌,但不能直接抑制其活性。芹菜素能抑制细胞粘附、运动,在40μmol/L时,抑制率分别为(30.80±3.00)%和(29.04±1.70)%,但抑制细胞体外侵袭作用不显著,仅为(12.08±0.50)%,且不能抑制MMP-9分泌也不能直接抑制其活性。结论:大黄素、芹菜素对人卵巢癌HO-8910PM细胞均有一定的毒性,而大黄素更具有成为抗肿瘤侵袭药物的潜力。 相似文献
3.
Ovarian cancer has the worst prognosis among all types of gynecological malignancies and patients are often diagnosed at an advanced stage with distant metastasis. In the present study, it was found that emodin, a small molecular chemical drug derived from natural plants, has antitumor effects on ovarian cancer cells. Emodin induced cytotoxicity and inhibited proliferation in the ovarian cancer cell lines, SK-OV-3, A2780 and PA-1. In addition, emodin inhibited the migration and invasion abilities of the ovarian cancer cells by inhibiting epithelial-mesenchymal transition (EMT), which was evidenced by the downregulation of N-cadherin and vimentin, and the upregulation of E-cadherin protein expression levels. When a subcutaneous xenograft SK-OV-3 tumor mouse model was used, emodin notably reduced the tumor growth rate and inhibited tumor cell proliferation. Furthermore, mechanical analysis revealed that emodin markedly inhibited EMT and reduced the stemness of tumor cells, which was evidenced by the decrease in the protein expression of CD133 and Oct4. Pulmonary metastasis of the ovarian cancer cells was significantly suppressed in the tumor mouse model by the administration of emodin. In addition, flow cytometry analysis indicated that emodin significantly reduced the proportion of ovarian cancer stem-like cells in metastatic lung tissues. In conclusion, emodin, a potent inhibitor of EMT, could serve as a potential candidate for ovarian cancer therapy. 相似文献
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Emodin (1, 3, 8-trihydroxy-6-methylanthraquinone) is an active constituent isolated from the root of Rheum palmatum L and is the main effective component of some Chinese herbs and plants. Pharmacological studies have demonstrated that emodin exhibits anti-cancer effects on several human cancers. However, the molecular mechanisms of emodin-mediated tumor regression have not been fully defined. This study was performed to investigate the antiproliferative and antimetastatic effects of emodin on pancreatic cancer in vitro and in vivo. Our results showed that emodin induced a higher percentage of growth inhibition and apoptosis in the pancreatic cancer cell line SW1990 compared to that of control, and emodin suppressed the migration and invasion of SW1990 cells in a dose-dependent manner. To investigate the possible mechanisms involved in these events, we performed electrophoretic mobility shift assay (EMSA) and Western blot analysis, and found that emodin significantly down-regulated NF-κB DNA-binding activity, survivin and MMP-9 in SW1990 cells. Moreover, the expression of cleaved caspase-3 was up-regulated in SW1990 cells after treatment with emodin. In addition, a metastatic model simulating human pancreatic cancer was established by orthotopic implantation of histologically intact human tumor tissue into the pancreatic wall of nude mice. Oral administration of emodin significantly decreased tumor weight and metastasis compared to control. Furthermore, the expression of NF-κB, survivin and MMP-9 were also suppressed in tumor tissues after treatment with emodin. Collectively, our results indicated that emodin exerts antiproliferative and antimetastatic activity on pancreatic cancer both in?vitro and in?vivo, which may be related to down-regulation of NF-κB and its regulated molecules such as survivin and MMP-9 proteins. Consequently, these results provide important insights into emodin as an anti-invasive agent for the therapy of human pancreatic cancer. 相似文献
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目的:探讨血小板接触对乳腺癌循环肿瘤细胞(circulating tumor cells,CTCs)侵袭和迁移能力的影响。方法:利用CytoQuestTM CR抓取乳腺癌患者血液中的循环肿瘤细胞,通过RT-PCR检测Wnt2基因表达水平。通过Western blot检测肿瘤细胞上皮细胞-间充质转化(epithelial-mesenchymal transition,EMT)以及NF-κB信号通路相关蛋白的表达情况。通过细胞划痕、Transwell实验检测血小板的直接接触对肿瘤细胞侵袭和迁移能力的影响。通过封闭乳腺癌细胞中NF-κB的表达,观察NF-κB信号通路在肿瘤细胞侵袭和迁移能力中的重要作用。结果:RT-PCR结果显示,乳腺癌患者血液中的CTCs内Wnt2基因高表达。Western blot结果显示,血小板与乳腺癌细胞的直接接触增加了肿瘤细胞的上皮间质化进程,并诱导激活了肿瘤细胞的NF-κB通路。细胞划痕和Transwell实验结果显示,与血小板共培养可促进乳腺癌细胞的侵袭和迁移。此外,通过封闭乳腺癌细胞中NF-κB基因,可以降低Wnt2的表达,抑制肿瘤细胞的上皮间质化进程,减弱乳腺癌细胞的侵袭和迁移能力。结论:血小板与肿瘤细胞的直接接触促进了乳腺癌循环肿瘤细胞的侵袭和迁移能力,封闭NF-κB信号通路可能是抑制乳腺癌循环肿瘤细胞侵袭和迁移能力的有效策略。 相似文献
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Ting-hua Hu Yu Yao Shuo Yu Li-li Han Wen-juan Wang Hui Guo Tao Tian Zhi-pin Ruan Xiao-min Kang Jing Wang Shu-hong Wang Ke-jun Nan 《Cancer letters》2014
Stromal cell-derived factor 1 (SDF-1) and its receptor, CXCR4, play an important role in angiogenesis and are associated with tumor progression. This study aimed to investigate the role of SDF-1/CXCR4-mediated epithelial–mesenchymal transition (EMT) and the progression of colorectal cancer (CRC) as well as the underlying mechanisms. The data showed that expression of CXCR4 and β-catenin mRNA and protein was significantly higher in CRC tissues than in distant normal tissues. CXCR4 expression was associated with β-catenin expression in CRC tissues, whereas high CXCR4 expression was strongly associated with low E-cadherin, high N-cadherin, and high vimentin expression, suggesting a cross talk between the SDF-1/CXCR4 axis and Wnt/β-catenin signaling pathway in CRC. In vitro, SDF-1 induced CXCR4-positive colorectal cancer cell invasion and EMT by activation of the Wnt/β-catenin signaling pathway. In contrast, SDF-1/CXCR4 axis activation-induced colorectal cancer invasion and EMT was effectively inhibited by the Wnt signaling pathway inhibitor Dickkopf-1. In conclusion, CXCR4-promoted CRC progression and EMT were regulated by the Wnt/β-catenin signaling pathway. Thus, targeting of the SDF-1/CXCR4 axis could have clinical applications in suppressing CRC progression. 相似文献
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Kairui Liu Xiaolin Wu Xian Zang Zejian Huang Zeyu Lin Wenliang Tan Xiang Wu Wenrou Hu Baoqi Li Lei Zhang 《Oncology research》2020,28(5):559-560
Overexpression of the tumor necrosis factor receptor-associated factor 4 (TRAF4) has been detected in many
cancer types and is considered to foster tumor progression. However, the role of TRAF4 in hepatocellular carcinoma (HCC) remains elusive. In this study, we found that TRAF4 was highly expressed in HCC cell lines and
HCC tissues compared with normal liver cell lines and adjacent noncancerous tissues. TRAF4 overexpression
in HCC tissues was correlated with tumor quantity and vascular invasion. In vitro studies showed that TRAF4
was associated with HCC cell migration and invasion. An in vivo study verified that TRAF4 overexpression facilitated metastasis in nude mice. In addition, overexpressed TRAF4 promoted the phosphorylation of
Akt and induced Slug overexpression, leading to downregulated E-cadherin and upregulated vimentin, while
silencing TRAF4 moderated the phosphorylation of Akt and repressed the expression of Slug, which resulted
in upregulated E-cadherin and downregulated vimentin. These effects were inversed after pretreatment of the
PI3K/Akt inhibitor LY294002 or overexpression of constitutively active Akt1. Our study demonstrated that
TRAF4 was involved in promoting HCC cell migration and invasion. The process was induced by the EMT
through activation of the PI3K/Akt signaling pathway. 相似文献
10.
Ya-ling Tang Xin Liu Shi-yu Gao Hao Feng Ya-ping Jiang Sha-sha Wang Jing Yang Jian Jiang Xiang-rui Ma Ya-jie Tang Yu Chen Xin-hua Liang 《Oncotarget》2015,6(11):9031-9044
The wild-type p53 induced phosphatase 1 (WIP1) is an oncogene overexpressed in a variety of human cancers. Here, we demonstrated that WIP1 silencing reduced MMP-9 and VEGF-C expression as well as migration and invasion of salivary adenoid cystic carcinoma (ACC) cells. Overexpression of MMP-9 or VEGF-C restored migration and invasion in WIP1 knockdown cells, indicating that MMP-9 and VEGF-C are downstream targets of WIP1 signaling. Levels of cyclin D1 and c-Myc, targets of Wnt/β-catenin pathway, were significantly decreased by WIP1 silencing. In addition, WIP1 expression was positively associated with metastasis and prognosis of ACC patients as well as with MMP-9 or VEGF-C in ACC tissues. 相似文献
11.
Emodin inhibits vascular endothelial growth factor-A-induced angiogenesis by blocking receptor-2 (KDR/Flk-1) phosphorylation 总被引:6,自引:0,他引:6
Kwak HJ Park MJ Park CM Moon SI Yoo DH Lee HC Lee SH Kim MS Lee HW Shin WS Park IC Rhee CH Hong SI 《International journal of cancer. Journal international du cancer》2006,118(11):2711-2720
Emodin (1,3,8-trihydroxy-6-methylanthraquinone), an active component in the root and rhizome of Rheum palmatum, is a tyrosine kinase inhibitor with a number of biological activities, including antitumor effects. Here, we examine the effects of emodin on vascular endothelial growth factor (VEGF)-A-induced angiogenesis, both in vitro and in vivo. In vitro, emodin dose-dependently inhibits proliferation, migration into the denuded area, invasion through a layer of Matrigel and tube formation of human umbilical vein endothelial cells (HUVECs) stimulated with VEGF-A. Emodin also inhibits basic fibroblast growth factor-induced proliferation and migration of HUVECs and VEGF-A-induced tube formation of human dermal microvascular endothelial cells. Specifically, emodin induces the cell cycle arrest of HUVECs in the G0/G1 phase by suppressing cyclin D1 and E expression and retinoblastoma protein phosphorylation, and suppresses Matrigel invasion by inhibiting the basal secretion of matrix metalloproteinase-2 and VEGF-A-stimulated urokinase plasminogen activator receptor expression. Additionally, emodin effectively inhibits phosphorylation of VEGF-A receptor-2 (KDR/Flk-1) and downstream effector molecules, including focal adhesion kinase, extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, Akt and endothelial nitric oxide synthase. In vivo, emodin strongly suppresses neovessel formation in the chorioallantoic membrane of chick and VEGF-A-induced angiogenesis of the Matrigel plug in mice. Our data collectively demonstrate that emodin effectively inhibits VEGF-A-induced angiogenesis in vitro and in vivo. Moreover, inhibition of phosphorylation of KDR/Flk-1 and downstream effector molecules is a possible underlying mechanism of the anti-angiogenic activity of emodin. Based on these data, we propose that an interaction of emodin with KDR/Flk-1 may be involved in the inhibitory function of emodin toward VEGF-A-induced angiogenesis in vitro and responsible for its potent anti-angiogenic in vivo. 相似文献
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Kallistatin has been recognized as an endogenous angiogenesis inhibitor and exerts pleiotropic effects in inhibiting tumor growth, migration, apoptosis, and inflammation. The purpose of the present study was to investigate the potential role and mechanisms of kallistatin in cervical cancer. We demonstrated that kallistatin
effectively inhibited cell proliferation and enhanced apoptosis in a dose-dependent manner. Additionally, kallistatin suppressed migration and invasion activities and markedly reduced the expression of matrix-degrading
metalloproteinases, progelatinase (MMP-2), MMP-9, and urokinase-type PA (uPA). Kallistatin reversed the
epithelial–mesenchymal transition (EMT) and caused the upregulation of epithelial markers such as E-cadherin
and inhibited mesenchymal markers such as N-cadherin and vimentin. Moreover, kallistatin led to a marked
decrease in the expression of vascular endothelial growth factor (VEGF) and HIF-1a. In a xenograft mouse
model, kallistatin treatment reduced tumor growth. Importantly, kallistatin strikingly impeded NF-kB activation by suppressing IkBk degradation and the level of phosphorylation of p65. Interestingly, similar to kallistatin, treatment with PDTC (an inhibitor of NF-kB) also attenuated cell invasion and migration. Taken together,
these findings suggest that kallistatin suppresses cervical cancer cell proliferation, migration, and EMT and
promotes cell apoptosis by blocking the NF-kB signaling pathway, suggesting that kallistatin may be a novel
therapeutic target for cervical cancer treatment. 相似文献
15.
Secreted Frizzled-related proteins inhibit motility and promote growth of human malignant glioma cells 总被引:9,自引:0,他引:9
Roth W Wild-Bode C Platten M Grimmel C Melkonyan HS Dichgans J Weller M 《Oncogene》2000,19(37):4210-4220
Cellular resistance to multiple proapoptotic stimuli and invasion of surrounding brain tissue by migrating tumor cells are main obstacles to an effective therapy for human malignant glioma. Here, we report that the Wnt family of embryonic differentiation genes modulate growth of malignant glioma cells in vitro and in vivo and inhibit cellular migration in vitro. sFRPs (soluble Frizzled-related proteins) are soluble proteins that bind to Wnt and interfere with Wnt signaling. We find that sFRP-1 and sFRP-2 are produced by the majority of longterm and ex vivo malignant glioma cell lines. Glioma cells that ectopically express sFRPs exhibit increased clonogenicity and enhanced resistance to serum starvation. In contrast, sFRPs do not modulate glioma cell susceptibility to apoptosis induced by the cytotoxic cytokines, CD95 (Fas/APO-1) ligand (CD95L) or Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL), or various cytotoxic drugs. sFRP-2 strongly promotes the growth of intracranial glioma xenografts in nude mice. In contrast, enhanced expression of sFRPs inhibits the motility of glioma cells in vitro. sFRP-mediated effects on glioma cells are accompanied by decreased expression and activity of matrix metalloproteinase-2 (MMP-2) and decreased tyrosine phosphorylation of beta-catenin. Thus, sFRPs promote survival under non-supportive conditions and inhibit the migration of glioma cells. We suggest that the regulation of these cellular processes involves expression of MMP-2 and tyrosine phosphorylation of beta-catenin. These data support a function for Wnt signaling and its modulation by sFRPs in the biology of human gliomas. Oncogene (2000) 19, 4210 - 4220 相似文献
16.
Jun Shan Ruan Huan Zhou Lin Yang Ling Wang Zong Sheng Jiang Hong Sun Shao Ming Wang 《Oncology research》2019,27(5):593-600
Transforming growth factor- 1 (TGF- 1)-induced epithelial–mesenchymal transition (EMT) of non-small cell
lung cancer (NSCLC) may contribute to tumor metastasis. TGF- 1-induced EMT in H1975 cells (a human
NSCLC cell line) resulted in the adoption of mesenchymal responses that were predominantly mediated via
the TGF- 1–integrin signaling pathway. Ursolic acid has been previously reported to inhibit tumor growth and
metastasis in several cancers. However, whether ursolic acid can attenuate TGF- 1-induced EMT in H1975
cells and its underlying mechanisms remain unknown. In this study, ursolic acid significantly attenuated the
TGF- 1-induced decrease in E-cadherin level and elevated the level of N-cadherin. Furthermore, ursolic acid
inhibited the mesenchymal-like responses in H1975 cells, including cell migration, invasion, and activity of
matrix metallopeptidase (MMP)-2 and -9. Finally, our new findings provided evidence that ursolic acid could
inhibit EMT in NSCLC through TGF- 1 signaling pathway-mediated integrin V 5 expression, and this might
be the potential mechanism of resveratrol on the inhibition of invasion and metastases in NSCLC. We conclude
that ursolic acid attenuated TGF- 1-induced EMT in H1975 cells and thus might be a promising therapeutic
agent for treating NSCLC. 相似文献
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Colon cancer is one of the most common cancers in the world. Epithelial-to-mesenchymal transition (EMT)
is a crucial step in tumor progression and is also involved in the acquisition of stem cell-like properties. Some
miRNAs have been shown to function as either tumor suppressors or oncogenes in colon cancer. Here we
investigated the role of miR-147 in the regulation of the stem cell-like traits of colon cancer cells. We observed
that miR-147 was downregulated in several colon cancer cell lines, and overexpressed miR-147 decreased
the expression of cancer stem cell (CSC) markers OCT4, SOX2, and NANOG in the colon cancer cell lines
HCT116 and SW480. Overexpressed miR-147 inhibited EMT by increasing the expression of epithelial
markers E-cadherin and -catenin while decreasing the expression of mesenchymal markers fibronectin and
vimentin. Moreover, activation of EMT by TGF- 1 treatment significantly counteracted the inhibitive effect of
miR-147 on the expression of CSC markers OCT4, SOX2, and NANOG, supporting the idea that overexpressing miR-147 inhibited stem cell-like traits by suppressing EMT in colon cancer. In addition, we found that
overexpressed miR-147 downregulated the expression of -catenin, c-myc, and survivin, which were related to
the Wnt/ -catenin pathway. Moreover, treatment of miR-147 mimic-transfected cells with the Wnt/ -catenin
pathway activator LiCl attenuated the inhibitive effect of the miR-147 mimic on the EMT and stem cell-like
traits of colon cancer cells, indicating that ectopic expression of miR-147 inhibited stem cell-like traits in colon
cancer cells by suppressing EMT via the Wnt/ -catenin pathway. In summary, our present study highlighted
the crucial role of miR-147 in the inhibition of the stem cell-like traits of colon cancer cells and indicated that
miR-147 could be a promising therapeutic target for colon cancer treatment. 相似文献
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