scholarly journals Total saponins from Rubus parvifolius L. inhibits cell proliferation, migration and invasion of malignant melanoma in vitro and in vivo

2020 ◽  
Author(s):  
Jinfeng Cao ◽  
Xue Zhao ◽  
Yan Ma ◽  
Jian Yang ◽  
Fuqiang Li
Keyword(s):  
Cell Proliferation ◽  
Malignant Melanoma ◽  
Melanoma Cell ◽  
Nude Mice ◽  
Melanoma Metastasis ◽  
Invasion And Migration ◽  
Rubus Parvifolius ◽  
And Migration

Background: Total saponins from Rubus parvifolius L. (TSRP) is the main bioactive fractions responsible for the antitumor activities. The work was aimed to evaluate the anti-tumor effect of TSRP in malignant melanoma in vitro and in vivo. Methods and Results: Anti melanoma cell proliferation, invasion and migration effect of TSRP were detected in human malignant melanoma A375 cells under the indicated time and dosages. In vivo anti-tumor effect of TSRP was measured in A375 xenograft immunodeficient nude mice. Sixty A375 xenografts were randomly divided into five groups: Vehicle, cyclophosphamide (CTX, 20 mg/kg), TSRP (25 mg/kg), TSRP (50 mg/kg) and TSRP (100 mg/kg) groups for 14 days’ treatment. In addition, the melanoma cell metastasis in lung in vivo of TSRP was detected in A375 tail vein injection mice, and the histopathalogical analysis of the metastasis lung was detected by H & E stating. TSRP was significantly inhibited the cell proliferation, invasion and migration of A375 in vitro at the indicated time and dosages. TSRP treatment was effectively blocked the tumor growth in immunodeficient nude mice. In addition, TSRP was also significantly inhibited the melanoma metastasis of lung. Conclusion: This study indicated that the TSRP has a remarkable anti malignant melanoma effect, which mainly through the inhibition of the cell invasion,migration and tumor metastasis.

Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration

2021 ◽  
pp. 1-9
Author(s):  
Huan Guo ◽  
Baozhen Zeng ◽  
Liqiong Wang ◽  
Chunlei Ge ◽  
Xianglin Zuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Lung Cancer Cells ◽  
Invasion And Migration ◽  
And Migration

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

MiR-134, Mediated by IRF1, Suppresses Tumorigenesis and Progression by Targeting VEGFA and MYCN in Osteosarcoma

2020 ◽  
Vol 20 (10) ◽  
pp. 1197-1208
Author(s):  
Zhuo Ma ◽  
Kai Li ◽  
Peng Chen ◽  
Qizheng Pan ◽  
Xuyang Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mrna Levels ◽  
Invasion And Migration ◽  
And Migration

Background: Osteosarcoma (OS) is a prevalent primary bone malignancy and its distal metastasis remains the main cause of mortality in OS patients. MicroRNAs (miRNAs) play critical roles during cancer metastasis. Objective: Thus, elucidating the role of miRNA dysregulation in OS metastasis may provide novel therapeutic targets. Methods: The previous study found a low miR-134 expression level in the OS specimens compared with paracancer tissues. Overexpression of miR-134 stable cell lines was established. Cell viability assay, cell invasion and migration assay and apoptosis assay were performed to evaluate the role of miR-134 in OS in vitro. Results: We found that miR-134 overexpression inhibits cell proliferation, migration and invasion, and induces cell apoptosis in both MG63 and Saos-2 cell lines. Mechanistically, miR-134 targets the 3'-UTR of VEGFA and MYCN mRNA to silence its translation, which was confirmed by luciferase-reporter assay. The real-time PCR analysis illustrated that miR-134 overexpression decreases VEGFA and MYCN mRNA levels. Additionally, the overexpression of VEGFA or MYCN can partly attenuate the effects of miR-134 on OS cell migration and viability. Furthermore, the overexpression of miR-134 dramatically inhibits tumor growth in the human OS cell line xenograft mouse model in vivo. Moreover, bioinformatic and luciferase assays indicate that the expression of miR-134 is regulated by Interferon Regulatory Factor (IRF1), which binds to its promoter and activates miR-134 expression. Conclusion: Our study demonstrates that IRF1 is a key player in the transcriptional control of miR-134, and it inhibits cell proliferation, invasion and migration in vitro and in vivo via targeting VEGFA and MYCN.

scholarly journals Long noncoding RNA LINC01111 suppresses pancreatic cancer aggressiveness by regulating DUSP1 expression via microRNA-3924

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Shutao Pan ◽  
Ming Shen ◽  
Min Zhou ◽  
Xiuhui Shi ◽  
Ruizhi He ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cell Invasion ◽  
Molecular Mechanisms ◽  
Invasion And Migration ◽  
Cancer Aggressiveness ◽  
And Migration

AbstractDysfunction in long noncoding RNAs (lncRNAs) is reported to participate in the initiation and progression of human cancer; however, the biological functions and molecular mechanisms through which lncRNAs affect pancreatic cancer (PC) are largely unknown. Here, we report a novel lncRNA, LINC01111, that is clearly downregulated in PC tissues and plasma of PC patients and acts as a tumor suppressor. We found that the LINC01111 level was negatively correlated with the TNM stage but positively correlated with the survival of PC patients. The overexpression of LINC01111 significantly inhibited cell proliferation, the cell cycle, and cell invasion and migration in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, the knockdown of LINC01111 enhanced cell proliferation, the cell cycle, and cell invasion and migration in vitro, as well as tumorigenesis and metastasis in vivo. Furthermore, we found that high expression levels of LINC01111 upregulated DUSP1 levels by sequestering miR-3924, resulting in the blockage of SAPK phosphorylation and the inactivation of the SAPK/JNK signaling pathway in PC cells and thus inhibiting PC aggressiveness. Overall, these data reveal that LINC01111 is a potential diagnostic biomarker for PC patients, and the newly identified LINC01111/miR-3924/DUSP1 axis can modulate PC initiation and development.

RNAi-mediated MMP-9 silencing inhibits mouse melanoma cell invasion and migration in vitro and in vivo

2013 ◽  
Vol 37 (8) ◽  
pp. 849-854 ◽  
Author(s):  
Zhao-Yong Tang ◽  
Yang Liu ◽  
Long-Xing Liu ◽  
Xiao-Yan Ding ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Melanoma Cell ◽  
Cell Invasion ◽  
Invasion And Migration ◽  
Mouse Melanoma ◽  
Mouse Melanoma Cell ◽  
And Migration

scholarly journals Functional Implication of Netrin Expression in Malignant Melanoma

2009 ◽  
Vol 31 (6) ◽  
pp. 415-422
Author(s):  
Simone Kaufmann ◽  
Silke Kuphal ◽  
Thomas Schubert ◽  
Anja K. Bosserhoff
Keyword(s):  
Malignant Melanoma ◽  
Melanoma Cells ◽  
Transcriptional Level ◽  
Altered Expression ◽  
Invasion And Migration ◽  
Expression Of Genes ◽  
Functional Relevance ◽  
And Migration

Background: Malignant melanoma cells are known to have altered expression of genes supporting proliferation and invasion, however, the expression of molecules of the Netrin family of repellent factors has not been analyzed in melanomas until now.Results: Here, we show that Netrin-1 expression is strongly induced in melanoma cells compared to melanocytes in vivo and in vitro controlled at the transcriptional level via ETS-1. In addition, the expression of the netrin receptor UNC5B was induced and that of UNC5C was reduced in the tumor cells. In order to determine the functional relevance of Netrin-1 expression in malignant melanoma, Netrin expression in melanoma cells was reduced by siRNA attempts and primary human melanocytes were treated with recombinant Netrin-1. The cells showed no changes in proliferation or apoptosis, however, a strong reduction of migratory properties was observed in the melanoma cells after reduction of Netrin expression whereas melanocyte migration was strongly induced by treatment with Netrin.Conclusions: Our study suggests that Netrin-1 promotes melanoma cell invasion and migration and therefore has an important role in the progression of malignant melanoma.

scholarly journals P2X7 promotes metastatic spreading and triggers release of miRNA-containing exosomes and microvesicles from melanoma cells

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Anna Pegoraro ◽  
Elena De Marchi ◽  
Manuela Ferracin ◽  
Elisa Orioli ◽  
Michele Zanoni ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Melanoma Cell ◽  
P2x7 Receptor ◽  
Metastatic Malignant Melanoma ◽  
Melanoma Cells ◽  
Vesicular Release ◽  
And Migration ◽  
Metastatic Spreading

AbstractTumor growth and metastatic spreading are heavily affected by the P2X7 receptor as well as microvesicles and exosomes release into the tumor microenvironment. P2X7 receptor stimulation is known to trigger vesicular release from immune and central nervous system cells. However, P2X7 role in microvesicles and exosomes delivery from tumor cells was never analyzed in depth. Here we show that P2X7 is overexpressed in patients affected by metastatic malignant melanoma and that its expression closely correlates with reduced overall survival. Antagonism of melanoma cell-expressed P2X7 receptor inhibited in vitro anchorage-independent growth and migration and in vivo dissemination and lung metastasis formation. P2X7 stimulation triggered the release of miRNA-containing microvesicles and exosomes from melanoma cells, profoundly altering the nature of their miRNA content, as well as their dimensions and quantity. Among the more than 200 miRNAs that we found up-or-down-modulated for each vesicular fraction tested, we identified three miRNAs, miR-495-3p, miR-376c-3p, and miR-6730-3p, that were enriched in both the exosome and microvesicle fraction in a P2X7-dependent fashion. Interestingly, upon transfection, these miRNAs promoted melanoma cell growth or migration, and their vesicular release was minimized by P2X7 antagonism. Our data unveil an exosome/microvesicle and miRNA-dependent mechanism for the pro-metastatic activity of the P2X7 receptor and highlight this receptor as a suitable prognostic biomarker and therapeutic target in malignant melanoma.

miR-92b-3p Promotes Colorectal Carcinoma Cell Proliferation, Invasion, and Migration by Inhibiting FBXW7 In Vitro and In Vivo

2018 ◽  
Vol 37 (5) ◽  
pp. 501-511 ◽  
Author(s):  
Lei Gong ◽  
Mingyang Ren ◽  
Zhenbing Lv ◽  
Yuling Yang ◽  
Ziwei Wang
Keyword(s):  
Cell Proliferation ◽  
Colorectal Carcinoma ◽  
Carcinoma Cell ◽  
Invasion And Migration ◽  
And Migration

scholarly journals Silencing of Prrx2 Inhibits the Invasion and Metastasis of Breast Cancer both In Vitro and In Vivo by Reversing Epithelial-Mesenchymal Transition

2017 ◽  
Vol 42 (5) ◽  
pp. 1847-1856 ◽  
Author(s):  
Zhi-Dong Lv ◽  
Hai-Bo Wang ◽  
Xiang-Ping Liu ◽  
Li-Ying Jin ◽  
Ruo-Wu Shen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Association Studies ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Node Metastasis ◽  
And Migration

Background/Aims: Epithelial-mesenchymal transition (EMT) is recognized as a crucial mechanism in breast cancer progression and metastasis. Paired-related homeobox 2 (Prrx2) has been identified as a new EMT inducer in cancer, but the underlying mechanisms are still poorly understood. Methods: The expression of Prrx2 was assessed by immunohistochemistry in breast cancer tissues to evaluate the clinicopathological significance of Prrx2, as well as the correlation between Prrx2 and EMT. Short hairpin RNA knockdown of Prrx2 was used to examine cellular effects of Prrx2, detecte the expression of Wnt/β-catenin signaling and EMT-associated proteins, and observe cell proliferation, invasion and migration abilities in vitro and in vivo. Results: Clinical association studies showed that Prrx2 expression was related to tumor size, lymph node metastasis, tumor node metastasis stages, EMT and poor survival. Results also showed that knockdown of Prrx2 could alter cell morphology, suppressed the abilities of cell proliferation, invasion and migration in breast cancer. Moreover, silencing of Prrx2 induced the mesenchymal-epithelial transition and prevented nuclear translocation of β-catenin, inhibited wnt/β-catenin signaling pathway. Conclusion: Our study indicated that Prrx2 may be an important activator of EMT in human breast cancer and it can serve as a molecular target of therapeutic interventions for breast cancer.

scholarly journals Mesenchymal stem cell-derived exosomal microRNA-133b suppresses glioma progression via Wnt/β-catenin signaling pathway by targeting EZH2

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Haiyang Xu ◽  
Guifang Zhao ◽  
Yu Zhang ◽  
Hong Jiang ◽  
Weiyao Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Glioma Cell ◽  
Expression Patterns ◽  
Glioma Cells ◽  
Invasion And Migration ◽  
Glioma Cell Proliferation ◽  
And Migration

Abstract Background Mesenchymal stem cells (MSCs) play a significant role in cancer initiation and metastasis, sometimes by releasing exosomes that mediate cell communication by delivering microRNAs (miRNAs). This study aimed to investigate the effects of exosomal miR-133b derived from MSCs on glioma cell behaviors. Methods Microarray-based analysis identified the differentially expressed genes (DEGs) in glioma. The expression patterns of EZH2 and miR-133b along with interaction between them were clarified in glioma. The expression of miR-133b and EZH2 in glioma cells was altered to examine their functions on cell activities. Furthermore, glioma cells were co-cultured with MSC-derived exosomes treated with miR-133b mimic or inhibitor, and EZH2-over-expressing vectors or shRNA against EZH2 to characterize their effect on proliferation, invasion, and migration of glioma cells in vitro. In vivo assays were also performed to validate the in vitro findings. Results miR-133b was downregulated while EZH2 was upregulated in glioma tissues and cells. miR-133b was found to target and negatively regulate EZH2 expression. Moreover, EZH2 silencing resulted in inhibited glioma cell proliferation, invasion, and migration. Additionally, MSC-derived exosomes containing miR-133b repressed glioma cell proliferation, invasion, and migration by inhibiting EZH2 and the Wnt/β-catenin signaling pathway. Furthermore, in vivo experiments confirmed the tumor-suppressive effects of MSC-derived exosomal miR-133b on glioma development. Conclusion Collectively, the obtained results suggested that MSC-derived exosomes carrying miR-133b could attenuate glioma development via disrupting the Wnt/β-catenin signaling pathway by inhibiting EZH2, which provides a potential treatment biomarker for glioma.

scholarly journals Isorhamnetin Induces Melanoma Cell Apoptosis via the PI3K/Akt and NF-κB Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Ran Duan ◽  
Xiao Liang ◽  
Bangda Chai ◽  
Yiwen Zhou ◽  
Hengyu Du ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Melanoma Cell ◽  
Cell Apoptosis ◽  
In Vitro Study ◽  
B16f10 Cell ◽  
Antitumor Effects ◽  
Melanoma Treatment ◽  
And Migration

Malignant melanoma is characterized by its bad prognosis for aggressiveness, drug resistance, and early metastasis. Isorhamnetin (3′-methoxy-3,4′,5,7-tetrahydroxyflavone; IH) is a natural flavonoid that has been investigated for its antitumor effects in breast cancer, colon cancer, and gastric cancer through inducing cell apoptosis. Given its role in tumor inhibition, no research has been conducted concerning its effect against melanoma. In the present study, we found that IH could significantly inhibit B16F10 cell proliferation and migration and induce B16F10 cell apoptosis. The examination on molecular mechanism revealed that IH could suppress the phosphorylation of Akt and the translocation of NF-κB, which are key factors in apoptosis-related pathways. We also detected that this process was related to the bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases 4 (PFKFB4) by PFKFB4 knockdown experiment. In line with in vitro study, we further provided that IH effectively inhibited tumor growth in vivo. Taken together, IH was proven to induce melanoma cell apoptosis in vitro and in vivo, which may serve as a potential agent in malignant melanoma treatment in the future.

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