Use of PG545, a heparanase inhibitor, to inhibit pancreatic cancer tumor cell proliferation and migration in vitro and in vivo.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 234-234
Author(s):  
Katherine Ostapoff ◽  
Niranjan Awasthi ◽  
Roderich Schwarz ◽  
Rolf A. Brekken
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Tumor Cell Proliferation ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

234 Background: Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to conventional chemotherapy, as result there is an ongoing search to find novel effective strategies. Resistance is due in part to the high proportion of stromal tissue within the primary tumor. This intricate ECM (extracellular matrix) includes heparan-sulfate glycosaminoglycans which participate in tumor progression, angiogenesis and metastasis. PG545 is a heparanase inhibitor developed to target these pathways. Methods: In vitro cell viability assays were performed using WST-1 reagent and migration was evaluated using T- scratch assay. Animal survival experiments were performed by intraperitoneal injection of AsPC-1 (0.75 x 10^6) cells. In vivo tumor growth experiments were performed by orthotopic injection of PanO2-HY (5x10^5) cells. Results: PG545 significantly inhibited proliferation of tumor cells (AsPC-1 and PanO2) and fibroblasts (WI-38). PG545 caused only a modest inhibition in endothelial cell (HUVECs) proliferation. Migration was significantly inhibited by 1 µM PG545 in AsPC-1 and PanO2 after 12 hours. In a metastatic model of pancreatic cancer, treatment with PG545 (10 mg/kg 1st week, 5 mg/kg 2nd week) improved survival (35 days) compared to saline (22 days) and gemcitabine (28 days). In an immunocompetent orthotopic model, mice treated with PG545 (5 mg/kg twice weekly) had significantly decreased tumor weights after 3 weeks of therapy (p=0.002). Total metastatic events were also reduced in PG545 compared to gemcitabine and control treatment in the PanO2 model. Conclusions: PG545 inhibits tumor cell proliferation and migration in vitro and prolongs survival and inhibits tumor growth in vivo. Additionally it inhibits metastasis in vivo. Further studies are underway to elucidate the mechanism of inhibition and changes to pancreatic tumor microenvironment.

scholarly journals Knockdown of LncRNA LINC00958 Inhibits the Proliferation and Migration of NSCLC Cells by MiR-204-3p/KIF2A Axis

2021 ◽  
Vol 30 ◽  
pp. 096368972110255
Author(s):  
Qing Wang ◽  
Kai Li ◽  
Xiaoliang Li
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Model ◽  
Luciferase Reporter ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Increasing evidence suggests that long non-coding RNAs (lncRNAs) function in the tumorigenesis of NSCLC. LINC00958, a newly identified lncRNA, has been reported to be closely linked to tumorigenesis in several cancers. However, its specific role in NSCLC remains unclear. In this study, we determined the expression of LINC00958 in NSCLC by RT-qPCR analysis and evaluated cell proliferation and migration by CCK-8 and transwell assays, respectively. We established a xenograft tumor model to examine the effect of LINC00958 on tumor growth in vivo. Luciferase reporter assays were performed to determine the interaction between LINC00958 and miR-204-3p and the interaction between miR-204-3p and KIF2A. We found that LINC00958 was up-regulated in NSCLC tissues and cell lines. Down-regulation of LINC00958 inhibited cell proliferation and migration in vitro and suppressed tumor growth in vivo. Besides, miR-204-3p was identified as a target of LINC00958 and miR-204-3p inhibitor could reverse the inhibitory effect of LINC00958 knockdown on proliferation and migration of NSCLC cells. We also validated that KIF2A, a direct target of miR-204-3p, was responsible for the biological role of LINC00958. KIF2A antagonized the effect of miR-204-3p on NSCLC cell proliferation and migration and was regulated by LINC00958/miR-204-3p. Taken together, these data indicate that the LINC00958/miR-204-3p/KIF2A axis is critical for NSCLC progression, which might provide a potential therapeutic target of NSCLC.

scholarly journals miR-26a/b Inhibit Tumor Growth and Angiogenesis by Targeting the HGF-VEGF Axis in Gastric Carcinoma

2017 ◽  
Vol 42 (4) ◽  
pp. 1670-1683 ◽  
Author(s):  
Yiran Si ◽  
Haiyang Zhang ◽  
Tao Ning ◽  
Ming Bai ◽  
Yi Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Luciferase Assay ◽  
Human Gastric Cancer ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Background/Aims: Abnormal expression of HGF is found in various cancers and correlates with tumor proliferation, metastasis and angiogenesis. However, the regulatory mechanism of the HGF-VEGF axis remains unclear. Methods: The expression characteristic of HGF in human gastric cancer tissues was shown by an immunohistochemistry assay, and the expression levels of target protein were detected by Western blot. The relative levels of miR-26a/b and target mRNA were examined by qRT-PCR. We used bioinformatics tools to search for miRNAs that can potentially target HGF. A luciferase assay was used to confirm direct targeting. Furthermore, the functions of miR-26a/b and HGF were evaluated by cell proliferation and migration assays in vitro and by the mouse xenograft tumor model in vivo. Results: We found that the HGF protein was clearly increased while miR-26a/b were dramatically down-regulated in gastric cancer. miR-26a/b directly bind to the 3’-UTR of HGF mRNA at specific targeting sites. We demonstrated that the repression of the HGF-VEGF pathway by miR-26a/b overexpression suppressed gastric cancer cell proliferation and migration. Furthermore, miR-26a/b also showed an anti-tumor effect in the xenograft mouse model by suppressing tumor growth and angiogenesis. Conclusions: miR-26a/b could suppress tumor tumorigenesis and angiogenesis by targeting the HGF-VEGF axis and could serve as a potential treatment modality for targeted therapy in the clinical treatment of gastric cancer.

scholarly journals Knockdown of lncRNA LINC00958 inhibits the proliferation and migration of NSCLC cells by miR-204-3p/KIF2A axis

2020 ◽  
Author(s):  
Guan-Bin Qi ◽  
Lei Li
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Luciferase Reporter ◽  
Cell Proliferation And Migration ◽  
Reporter Assays ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: LINC00958, a newly identified lncRNA, has been reported to be closely linked to tumorigenesis in multiple cancers. However, its specific role in non-small cell lung cancer (NSCLC) remains unclear.Methods: The expression of LINC00958 was determined by RT-qPCR analysis. Cell proliferation and migration were evaluated by CCK-8 and transwell assays, respectively. Xenograft tumor models were established to examine the effect of LINC00958 on tumor growth in vivo. Luciferase reporter assays were performed to determine the interaction between LINC00958 and miR-204-3p and the interaction between miR-204-3p and KIF2A.Results: We found that LINC00958 was up-regulated in NSCLC tissues and cell lines. Down-regulation of LINC00958 inhibited cell proliferation and migration in vitro and suppressed tumor growth in vivo. Mechanically, we revealed that LINC00958 influenced NSCLC progression partly by sponging miR-204-3p and regulating KIF2A expression.Conclusions: Our study provided new insights into the role of LINC00958 as a promising prognostic biomarker and a therapeutic target for NSCLC.

scholarly journals Long Non-coding RNA X-Inactive Specific Transcript Mediates Cell Proliferation and Intrusion by Modulating the miR-497/Bcl-w Axis in Extranodal Natural Killer/T-cell Lymphoma

2020 ◽  
Vol 8 ◽  
Author(s):  
Qinhua Liu ◽  
Ruonan Ran ◽  
Zhengsheng Wu ◽  
Xiaodan Li ◽  
Qingshu Zeng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Natural Killer T Cell ◽  
Cell Proliferation And Migration ◽  
Non Coding Rna ◽  
And Migration ◽  
Long Non Coding Rna ◽  
Killer T Cell ◽  
Proliferation And Migration

The present study was directed toward laying new findings for Extranodal natural killer/T-cell lymphoma (ENKL)-oriented therapy with a focus on long non-coding RNA (lncRNA)–microRNAs (miRNAs)–mRNA interaction. The expression and function of XIST (X-inactive specific transcript) were analyzed both in vivo and in vitro. The online database of lncRNA-miRNA interaction was used to screen the target of XIST, and miR-497 was selected. Next, the predicted binding between XIST and miR-497, and the dynamic effect of XIST and miR-497 on downstream Bcl-w was evaluated. We found that XIST dramatically increased in the blood of ENKL patients and cell lines. XIST knockdown suppressed the cell proliferation and migration in vivo and in vitro. Herein, we confirmed the negative interaction between XIST and miR-497. Moreover, XIST knockdown reduced the protein levels of Bcl-w, a downstream target of miR-497. XIST sponges miR-497 to promote Bcl-w expression, and finally modulating ENKL cell proliferation and migration. To be interested, inhibition of Bcl-w by ABT737 can overcome the high expression of XIST, and suppressed the ENKL proliferation and migration by inducing apoptosis. This study provided a novel experimental basis for ENKL-oriented therapy with a focus on the lncRNA–miRNA–mRNA interaction.

scholarly journals Metformin Suppressed CXCL8 Expression and Cell Migration in HEK293/TLR4 Cell Line

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Zhihui Xiao ◽  
Wenjun Wu ◽  
Vladimir Poltoratsky
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Tumor Cell ◽  
Nuclear Translocation ◽  
High Dose ◽  
Dependent Manner ◽  
Tumor Cell Proliferation ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Chronic inflammation is associated with cancer. CXCL8 promotes tumor microenvironment construction through recruiting leukocytes and endothelial progenitor cells that are involved in angiogenesis. It also enhances tumor cell proliferation and migration. Metformin, type II diabetes medication, demonstrates anticancer properties via suppressing inflammation, tumor cell proliferation, angiogenesis, and metastasis. This study intended to address the role of metformin in regulation of CXCL8 expression and cell proliferation and migration. Our data indicated that metformin suppressed LPS-induced CXCL8 expression in a dose-dependent manner through inhibiting NF-κB, but not AP-1 and C/EBP, activities under the conditions we used. This inhibitory effect of metformin is achieved through dampening LPS-induced NF-κB nuclear translocation. Cell migration was inhibited by metformin under high dose (10 mM), but not cell proliferation.

scholarly journals MicroRNA-181a-5p Impedes IL-17-Induced Nonsmall Cell Lung Cancer Proliferation and Migration through Targeting VCAM-1

2017 ◽  
Vol 42 (1) ◽  
pp. 346-356 ◽  
Author(s):  
Yang Cao ◽  
Dan Zhao ◽  
Ping Li ◽  
Lanrong Wang ◽  
Bingli Qiao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Cell Lung Cancer ◽  
Nonsmall Cell Lung Cancer ◽  
Interleukin 17 ◽  
Tumor Cell Proliferation ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Aim: The contribution of the inflammatory mediator interleukin-17 (IL-17) in nonsmall cell lung cancer (NSCLC) malignancy has been reported in the literature. MicroRNA-181a-5p (miR-181a-5p) acts as a tumor suppressor which can regulate target gene at the posttranscriptional level. Our study aimed to investigate the interaction between IL-17 and miR-181a-5p in NSCLC. Methods: 35 patients with NSCLC and 24 COPD controls were selected and examined in our study. In vitro, H226 and H460 cell lines were exposed to different doses (20, 40, 60, and 80 ng/mL) of IL-17 to examine the effect of IL-17 on miR-181a-5p and vascular cell adhesion molecule 1 (VCAM-1) expression. MiR-181 mimic and miR-181a-5p inhibitor were transfected to explore the regulation of VCAM-1 as well as tumor cell proliferation and migration. Results: miR-181a-5p expression was downregulated, and IL-17 and VCAM-1 expression was upregulated in NSCLC tissues. Furthermore, IL-17 decreased miR-181a-5p expression but increased VCAM-1 expression in H226 and H460 cells. MiR-181 regulated VCAM-1 expression through binding to 3’-UTR sequence. MiR-181 attenuated tumor cell proliferation and migration. IL-17 modulated miR-181a-5p expression through activating NF-κB but not Stat3. Conclusion: Taken together, our data show the regulation of VCAM-1 expression by miR-181a-5p under IL-17 exposure, predicting a potential way for counteracting cancer metastasis.

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