scholarly journals Niclosamide Suppresses Migration and Invasion of Human Osteosarcoma Cells by Repressing TGFBI Expression via the ERK Signaling Pathway

2022 ◽  
Vol 23 (1) ◽  
pp. 484
Author(s):  
Liang-Tsai Yeh ◽  
Chiao-Wen Lin ◽  
Ko-Hsiu Lu ◽  
Yi-Hsien Hsieh ◽  
Chao-Bin Yeh ◽  
...  

Osteosarcoma is a highly common malignant bone tumor. Its highly metastatic properties are the leading cause of mortality for cancer. Niclosamide, a salicylanilide derivative, is an oral antihelminthic drug of known anticancer potential. However, the effect of niclosamide on osteosarcoma cell migration, invasion and the mechanisms underlying have not been fully clarified. Therefore, this study investigated niclosamide’s underlying pathways and antimetastatic effects on osteosarcoma. In this study, U2OS and HOS osteosarcoma cell lines were treated with niclosamide and then subjected to assays for determining cell migration ability. The results indicated that niclosamide, at concentrations of up to 200 nM, inhibited the migration and invasion of human osteosarcoma U2OS and HOS cells and repressed the transforming growth factor beta-induced protein (TGFBI) expression of U2OS cells, without cytotoxicity. After TGFBI knockdown occurred, cellular migration and invasion behaviors of U2OS cells were significantly reduced. Moreover, niclosamide significantly decreased the phosphorylation of ERK1/2 in U2OS cells and the combination treatment of the MEK inhibitor (U0126) and niclosamide resulted in the intensive inhibition of the TGFBI expression and the migratory ability in U2OS cells. Therefore, TGFBI derived from osteosarcoma cells via the ERK pathway contributed to cellular migration and invasion and niclosamide inhibited these processes. These findings indicate that niclosamide may be a powerful preventive agent against the development and metastasis of osteosarcoma.

2009 ◽  
Vol 28 (6) ◽  
pp. 347-353 ◽  
Author(s):  
Rogelio Zamilpa ◽  
Rajesha Rupaimoole ◽  
Clyde F. Phelix ◽  
Maria Somaraki-Cormier ◽  
William Haskins ◽  
...  

2017 ◽  
Vol 43 (1) ◽  
pp. 320-330 ◽  
Author(s):  
Wei Wang ◽  
Xiao Li ◽  
Fan-Bin Meng ◽  
Zhen-Xing Wang ◽  
Ren-Tao Zhao ◽  
...  

Background/Aims: This study aimed to explore the effects of the long non-coding RNA HOST2 (lnc-HOST2) on the proliferation, migration, invasion and apoptosis of osteosarcoma cells. Methods: Osteosarcoma tissues and adjacent normal tissues from 52 patients were selected. Human osteosarcoma cell lines (SaOS2, HOS, U2OS and MG-63) were collected and cultured; MG-63 cells had the highest lnc-HOST2 expression and thus were used in subsequent experiments. Then, MG-63 cells were transfected and divided into the blank (no transfection), si-CON (transfected with negative control siRNA) and si-lnc-HOST2 (transfected with small interference lnc-HOST2 siRNA) groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression of lnc-HOST2 in primary tissues and cells. Cell growth was detected using the CCK-8 and colony formation assays. Cell doubling time was detected. Cell migration and invasion were observed using the scratch test and Transwell assays. Cell apoptosis and cell cycle progression of osteosarcoma cells were detected using flow cytometry with annexin V/PI double staining and PI staining, respectively. Results: The level of lnc-HOST2 expression in the si-lnc-HOST2 group was significantly decreased compared to that in the blank and si-CON groups. The OD values in the si-lnc-HOST2 group were significantly lower than those in the blank and si-CON groups. Compared to the blank and si-CON groups, the si-lnc-HOST2 group presented significant decreases in the colony number and healing rates after scratching. The number of invasive cells in the si-lnc-HOST2 group was significantly less than that in the blank and si-CON groups. In the si-lnc-HOST2 group, the cell cycle was mainly halted in the G1 phase, and the apoptosis rate and doubling time in this group were significantly higher than those in the blank group and si-CON group. Conclusions: Inhibition of lnc-HOST2 could suppress the proliferation, migration, and invasion and promote the apoptosis of osteosarcoma cells.


2021 ◽  
Vol 14 (3) ◽  
pp. 260
Author(s):  
Yi-Hsien Hsieh ◽  
Wen-Hung Hsu ◽  
Shun-Fa Yang ◽  
Chung-Jung Liu ◽  
Ko-Hsiu Lu ◽  
...  

Timosaponin AIII (TSAIII) is a steroidal saponin which demonstrates anti-tumour activities. However, the effect of TSAIII on human osteosarcoma cells remains largely unknown. In this study, we demonstrated that TSAIII exerted a significant inhibitory effect on the distribution of cytoskeletal F-actin and cytoskeletal-related proteins, which contributed to the suppression of cell migration and invasion, without inhibiting cell growth or apoptosis. In the synergistic inhibitory analysis, cotreatment of TSAIII with αVβ3 integrin inhibitor [Cyclo(RGDyK)] or focal adhesion kinase (FAK) inhibitor (PF-573228) exerted greater synergistic inhibitory effects on the expression of Intergin αVβ3/FAK/cofilin axis, thus inhibiting the migration and invasion capacities of human osteosarcoma cells. TSAIII was demonstrated to significantly inhibit the pulmonary metastasis formation of human osteosarcoma cells in vivo in metastasis animal models. These findings reveal the inhibitory effects of TSAIII on the metastasis progression of human osteosarcoma cells and the regulation of integrin-αVβ3-FAK-Src and TESK1/p-cofilin mediated cytoskeletal F-actin pathway. Therefore, TSAIII might represent a novel strategy for the auxiliary treatment of human osteosarcoma cells.


2016 ◽  
Vol 11 (4) ◽  
pp. 1934578X1601100 ◽  
Author(s):  
Jose M. Moran ◽  
Olga Leal-Hernandez ◽  
Maria L. Canal-Macías ◽  
Raul Roncero-Martin ◽  
Rafael Guerrero-Bonmatty ◽  
...  

In this study, we evaluated the antiproliferative activity on two human osteosarcoma cell lines (MG-63 and Saos2) of oleuropein, an olive oil compound traditionally found in the Mediterranean diet. Oleuropein exhibited obvious cytotoxic effects on human osteosarcoma cells in a concentration- and time-dependent manner. Statistical analysis of IC50 by the Probit regression method suggested that oleuropein had similar toxic effects on both cell lines tested (IC50 range from 247.4–475.0 μM for MG63 cells and from 798.7–359.9 μM for Saos2 cells).


2017 ◽  
Vol 36 (9) ◽  
pp. 775-780 ◽  
Author(s):  
Xiaozhou Liu ◽  
Xing Zhou ◽  
Haidong Xu ◽  
Zhiwei He ◽  
Xin Shi ◽  
...  

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