Sufentanil Inhibits the Proliferation and Metastasis of Esophageal Cancer by Inhibiting the NF-κB and Snail Signaling Pathways

Sufentanil is a μ-opioid receptor agonist, widely used in intraoperative and postoperative analgesia of esophageal cancer. This study investigated the effects of sufentanil on the proliferation, invasion, and metastasis of esophageal carcinoma cells and its molecular mechanisms. Human esophageal carcinoma cells CaES-17 and Eca-109 were cultured in vitro. Different concentrations of sufentanil (1 and 10 μmol/L) were added to the experimental group. MTT was used to detect the proliferative activity of esophageal carcinoma cells. The migration ability of esophageal carcinoma cells was measured by the scratch test. Transwell was used to detect the invasive ability of esophageal carcinoma cells. The EMT marker expression was detected by qPCR. Meanwhile, effects of sufentanil on NF-κB and Snail expression and nucleation were evaluated. Establish a subcutaneous xenograft tumor model of nude mice with esophageal carcinoma cells and evaluate the antitumor effect of sufentanil. Sufentanil can inhibit the proliferation, invasion, and migration of CaES-17 and Eca-109 cells and has a dose-dependent relationship. The molecular mechanism showed that sufentanil could upregulate the expression of E-cadherin and inhibit the expression of vimentin. Sufentanil can inhibit the expression of NF-κB and Snail, as well as the nuclear expression of NF-κB and Snail. Xenograft tumor model results showed that sufentanil could inhibit tumor proliferation and NF-κB and Snail expression in tumor tissues of nude mice. Sufentanil inhibits esophageal cancer epithelial-mesenchymal transition (EMT) by acting on NF-κB and Snail signaling pathways to inhibit proliferation and metastasis of esophageal cancer.

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ANP32A promotes the proliferation, migration and invasion of hepatocellular carcinoma by modulating the HMGA1/STAT3 pathway

Carcinogenesis ◽

10.1093/carcin/bgaa138 ◽

2020 ◽

Author(s):

Zilu Tian ◽

Zhiyi Liu ◽

Xiaokang Fang ◽

Kuan Cao ◽

Bin Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Nude Mice ◽

High Mobility ◽

Tumor Model ◽

Migration And Invasion ◽

Xenograft Tumor ◽

Stat3 Pathway ◽

Xenograft Tumor Model ◽

Rna Immunoprecipitation ◽

Hcc Cells

Abstract ANP32A (acidic leucine-rich nuclear phosphoprotein-32A) has been reported to play an essential role in the development and progression of various human cancers. However, its expression pattern and possible mechanism in human hepatocellular carcinoma (HCC) remain to be elucidated. In this study, we used western blot and immunohistochemical staining to detect protein expression. The effects of ANP32A on the proliferation, migration and invasion of HCC cells were examined using 5-ethynyl-20-deoxyuridine (EdU), colony formation, CCK-8, and transwell assays. RT-qPCR was performed to detect mRNA expression. The interaction between ANP32A and the high mobility group A1 (HMGA1) mRNA was assessed using RNA immunoprecipitation (RIP). The tumorigenicity of ANP32A was assessed by establishing a xenograft tumor model in Balb/c nude mice. We found that the ANP32A protein was expressed at high levels in patients with HCC, which was associated with a poor prognosis. Functional experiments revealed that the silencing of ANP32A inhibited the proliferation, migration, and invasion of HCC cells, whereas overexpression of ANP32A promoted these processes. Further investigations indicated that ANP32A bound the HMGA1 mRNA and maintained its stability to promote the expression of HMGA1, thereby increasing the expression and activation of STAT3. Finally, a xenograft tumor model of Balb/c nude mice confirmed the tumorigenicity of ANP32A. This study found that ANP32A is up-regulated in patients with HCC and may accelerate the proliferation, migration, and invasion of HCC cells by modulating the HMGA1/STAT3 pathway.

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CNTO859, a Humanized Monoclonal Anti-Tissue Factor Antibody, Inhibits Experimental Tumor Growth in a BxPC-3 Human Pancreatic Adenocarcinoma Xenograft Tumor Model

Journal of Immunotherapy ◽

10.1097/00002371-200411000-00045 ◽

2004 ◽

Vol 27 (6) ◽

pp. S11

Author(s):

Richard Tawadros ◽

Cam Ngo ◽

Francis McCabe ◽

Marian Nakada ◽

G Mark Anderson

Keyword(s):

Tumor Growth ◽

Tissue Factor ◽

Pancreatic Adenocarcinoma ◽

Tumor Model ◽

Xenograft Tumor ◽

Experimental Tumor ◽

Human Pancreatic Adenocarcinoma ◽

Xenograft Tumor Model

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Wnt5b-induced PCP/JNK Activation Promotes PD-L1 Expression and the Malignant Phenotype of Non-small Cell Lung Cancer

10.21203/rs.3.rs-74120/v1 ◽

2020 ◽

Author(s):

Guangping Wu ◽

Yuan Luo ◽

Yusai Xie ◽

Yang Han ◽

Di Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Tumor Model ◽

Small Cell ◽

Xenograft Tumor ◽

Small Cell Lung ◽

Malignant Phenotype ◽

Membrane Recruitment ◽

Xenograft Tumor Model

Abstract Background: Wnt5b is noncanonical Wnt ligand, and programmed-death ligand 1 (PD-L1) is a targeted agent for immunotherapy, but the mechanism by which Wnt5b regulates PD-L1 expression in non-small cell lung cancer (NSCLC) is unclear. Methods: Wnt5b and PD-L1 expressions were detected in NSCLC specimens by immunohistochemistry. The interrelationship connecting Wnt5b with PD-L1 was verified using dual-luciferase assay, immunofluorescence, coimmunoprecipitation, western blot，real-time PCR and xenograft tumor model. Results: Wnt5b and PD-L1 expressions were positively correlated in NSCLC specimens. Five-year survival time in the group with their coexpression was significantly lower than that without coexpression. Under the effect of Wnt5b, Frizzled-3 (Fzd3) initiated Dishevellde-3 (Dvl-3) membrane recruitment via DEP domain by Dvl-3 phosphorylation, contributing to activate PCP/JNK signaling through the small GTPase Rac1, and then upregulate PD-L1 expression and promote the malignant phenotype of NSCLC in vivo and in vitro. After PD-L1 antibody treatment, Wnt5b induced tumor growth was inhibited significantly in xenograft tumor model. Conclusion: We demonstrate a new signal transduction pathway: Wnt5b initiates Dvl-3 membrane recruitment via DEP domain by Fzd3 so as to promote Rac1–PCP/JNK–PD-L1 pathway, which provides a potential target for clinical intervention and immunotherapy in lung cancer.

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Scanning Acoustic Microscopy—A Novel Noninvasive Method to Determine Tumor Interstitial Fluid Pressure in a Xenograft Tumor Model

Translational Oncology ◽

10.1016/j.tranon.2016.03.009 ◽

2016 ◽

Vol 9 (3) ◽

pp. 179-183 ◽

Cited By ~ 5

Author(s):

Matthias Hofmann ◽

Ralph Pflanzer ◽

Anowarul Habib ◽

Amit Shelke ◽

Jürgen Bereiter-Hahn ◽

...

Keyword(s):

Interstitial Fluid ◽

Fluid Pressure ◽

Tumor Model ◽

Interstitial Fluid Pressure ◽

Acoustic Microscopy ◽

Scanning Acoustic Microscopy ◽

Xenograft Tumor ◽

Noninvasive Method ◽

Xenograft Tumor Model ◽

Tumor Interstitial Fluid

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Use of Size and a Copolymer Design Feature To Improve the Biodistribution and the Enhanced Permeability and Retention Effect of Doxorubicin-Loaded Mesoporous Silica Nanoparticles in a Murine Xenograft Tumor Model

ACS Nano ◽

10.1021/nn200809t ◽

2011 ◽

Vol 5 (5) ◽

pp. 4131-4144 ◽

Cited By ~ 335

Author(s):

Huan Meng ◽

Min Xue ◽

Tian Xia ◽

Zhaoxia Ji ◽

Derrick Y. Tarn ◽

...

Keyword(s):

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Design Feature ◽

Tumor Model ◽

Xenograft Tumor ◽

Enhanced Permeability And Retention ◽

Xenograft Tumor Model

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201. Replication Deficient Adenovirus Carrying Apolipoprotein (a) Kringles Suppress Tumor Growth in NSCLC Xenograft Tumor Model

Molecular Therapy ◽

10.1016/s1525-0016(16)44407-2 ◽

2007 ◽

Vol 15 ◽

pp. S76

Keyword(s):

Tumor Growth ◽

Tumor Model ◽

Xenograft Tumor ◽

Apolipoprotein A ◽

Xenograft Tumor Model

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miR-9-5p Promotes β-Catenin-Activated Epithelial-To-Mesenchymal Transition of Triple-Negative Breast Cancer Via Targeting LZTS2

10.21203/rs.3.rs-105343/v1 ◽

2020 ◽

Author(s):

Jie Zhang ◽

Lina Zhang ◽

Jianlong Wang ◽

Jing Zhao ◽

Xuelian Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Suppressor ◽

Triple Negative Breast Cancer ◽

Nuclear Export ◽

Triple Negative ◽

Tumor Model ◽

Migration And Invasion ◽

Xenograft Tumor ◽

Xenograft Tumor Model ◽

Low Expression

Abstract Background: Leucine zipper tumor suppressor 2 (LZTS2), an emerging tumor-suppressor, is attenuated in multiple cancers including prostate, lung and colon cancer. However, its expression and upstream regulatory mechanisms in triple negative breast cancer (TNBC) still remain unknown.Materials and methods: The expression of LZTS2 in TNBC and matched para-carcinoma tissues was detected with immunohistochemistry. The correlations between LZTS2 expression and clinicopathological parameters were analyzed. Kaplan-Meier analysis was performed to determine the prognostic role of LZTS2 for TNBC patients. CCK-8, wound healing and transwell assay were used to detect the effect of LZTS2 overexpression on the proliferation, migration and invasion ability, respectively. The bioinformation algorithms were used to reveal the potential upstream regulatory miRNA. Then, dual-luciferase reporter assay was performed to confirm the regulatory effect of the chosen miRNA on the expression of LZTS2. miR-9-5p inhibitor was used to determine the effect of miR-9-5p on the subcellular localization of β-catenin. Then, western blotting was performed to reveal the effect of miR-9-5p on EMT-related proteins in TNBC cells. Xenograft tumor model was established to reveal the effect of miR-9-5p on TNBC progression in vivo.Results: Low expression of LZTS2 was observed in 62 of 95 cases of TNBC tissue. Low expression of LZTS2 was correlated with poor postoperative DFS and OS of TNBC patients. LZTS2 could inhibit the proliferation, migration and invasion ability of TNBC cells. LZTS2 could be downregulated by miR-9-5p in TNBC, and the nuclear export of β-catenin was suppressed. Consequently, miR-9-5p inhibitor downregulated E-cadherin and upregulated N-cadherin, Twist and Vimentin in TNBC cells. Xenograft tumor model showed that miR-9-5p inhibitor could upregulate the expression of LZTS2 and induce nuclear export of β-catenin in TNBC.Conclusions: miR-9-5p contributes to β-catenin-activated EMT via downregulating LZTS2, and thus promotes TNBC progression.

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TUFT1 promotes metastasis and chemoresistance in triple negative breast cancer through the TUFT1/Rab5/Rac1 pathway

Cancer Cell International ◽

10.1186/s12935-019-0961-4 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Weiguang Liu ◽

Jianjun Han ◽

Sufang Shi ◽

Yuna Dai ◽

Jianchao He

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Multivariate Analyses ◽

Tumor Model ◽

Rab Gtpase ◽

Xenograft Tumor ◽

Mechanistic Studies ◽

Xenograft Tumor Model

Abstract Background Triple negative breast cancer (TNBC) is a breast cancer (BC) subtype that is characterized by its strong invasion and a high risk of metastasis. However, the specific mechanisms underlying these phenotypes are unclear. TUFT1 plays an important role in BC and impacts the proliferation and survival of BC cells. Recent studies have shown that TUFT1 mediates intracellular lysosome localization and vesicle transport by regulating Rab GTPase, but the relevance of this activity in TNBC is unknown. Therefore, our aim was to systematically study the role of TUFT1 in the metastasis and chemoresistance of TNBC. Methods We measured TUFT1, Rab5-GTP, and Rac1-GTP expression levels in samples of human TNBC by immunohistochemistry (IHC) and conducted univariate and multivariate analyses. shRNA-mediated knockdown and overexpression, combined with transwell assays, co-immunoprecipitation, a nude mouse xenograft tumor model, and GTP activity assays were used for further mechanistic studies. Results TUFT1 expression was positively correlated with Rab5-GTP and Rac1-GTP in the TNBC samples, and co-expression of TUFT1 and Rab5-GTP predicted poor prognosis in TNBC patients who were treated with chemotherapy. Mechanism studies showed that TUFT1 could activate Rab5 by binding to p85α, leading to activation of Rac1 through recruitment of Tiam1, and concurrent down-regulation of the NF-κB pathway and proapoptotic factors, ultimately promoting metastasis and chemoresistance in TNBC cells. Conclusions Our findings suggest that the TUFT1/Rab5/Rac1 pathway may be a potential target for the effective treatment of TNBC.

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