Vascular endothelial growth factor-C modulates proliferation and chemoresistance in acute myeloid leukemic cells through an endothelin-1-dependent induction of cyclooxygenase-2

Hua, Kuo Tai; Lee, Wei Jiunn; Yang, Shun Fa; Chen, Chi Kuan; Hsiao, Michael; Ku, Chia-Chi; Lin, Wei; Kuo, Min Liang; Chien, Ming Hsien

doi:10.1016/j.bbamcr.2013.10.015

Cited by 23 publications

(18 citation statements)

References 45 publications

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“…ET-1 levels in SMMC-7221 cells were downregulated via the introduction of targeted ET-1 shRNA. The results of the present study demonstrated that silencing ET-1 inhibited the proliferation of SMMC-7221 cells and tumor growth, which is concurrent with the findings of previous studies (22,26,27).…”

Section: Discussionsupporting

confidence: 81%

Functions of endothelin-1 in apoptosis and migration in hepatocellular carcinoma

Shi

Zhou

Chen

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality in China and the third leading cause of cancer mortality worldwide. The mechanisms involved in the development and progression of HCC are not well understood. In the present study, the functions of endothelin-1 (ET-1) in HCC were studied and its underlying mechanisms were investigated. ET-1, B-cell lymphoma 2 (Bcl-2), Bcl-2 related protein 4 (Bax), matrix metalloproteinase (MMP)-2 and MMP-9 expression was measured by reverse transcription-quantitative polymerase chain reaction and western blotting. Cell proliferation was measured via Cell Counting kit-8 assay. Flow cytometry was performed for cell cycle and apoptosis analysis. Migration was measured via Transwell assay. The results demonstrated that ET-1 expression significantly increased in HCC tissues compared with the normal tissues of patients in The Cancer Genome Atlas dataset (P<0.01). Furthermore, downregulation of ET-1 was able to significantly inhibit cell proliferation and growth in vitro (P<0.01) and in vivo (P<0.01), and induce cell cycle arrest (P<0.05) and apoptosis (P<0.01) in the HCC SMMC-7721 cell line. Bioinformatics analysis demonstrated that the cell apoptosis signaling pathway was activated by ET-1. The ratio of B-cell lymphoma (Bcl-2) -related protein 4 (Bax)/Bcl-2 was significantly increased by downregulation of ET-1 (P<0.01). ET-1 downregulation also inhibited migration of SMMC-7721 cells (P<0.05) via decreasing levels of matrix metalloproteinase (MMP) -2 (P<0.05) and MMP-9 (P>0.05). These results suggest that ET-1 may be able to affect the apoptosis and migration of HCC cells via modulation of the Bax/Bcl-2 ratio and expression levels of MMP-2 and MMP-9, which indicates that ET-1 maybe a potential novel target for HCC treatment.

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Section: Discussionsupporting

confidence: 81%

Functions of endothelin-1 in apoptosis and migration in hepatocellular carcinoma

Shi

Zhou

Chen

et al. 2017

Experimental and Therapeutic Medicine

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“…Emerging evidence indicates that the VEGF ligands act as survival factors for tumour cells that express the receptors343536. In leukaemia cells, the VEGF family opposes apoptosis via induction of the anti-apoptotic protein Bcl-2 and blockade of VEGFR3 induces chemosensitisation in ovarian cancer cells3738.…”

Section: Resultsmentioning

confidence: 99%

Blockade of vascular endothelial growth factor receptors by tivozanib has potential anti-tumour effects on human glioblastoma cells

Momeny

Moghaddaskho

Gortany

et al. 2017

Sci Rep

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Glioblastoma (GBM) remains one of the most fatal human malignancies due to its high angiogenic and infiltrative capacities. Even with optimal therapy including surgery, radiotherapy and temozolomide, it is essentially incurable. GBM is among the most neovascularised neoplasms and its malignant progression associates with striking neovascularisation, evidenced by vasoproliferation and endothelial cell hyperplasia. Targeting the pro-angiogenic pathways is therefore a promising anti-glioma strategy. Here we show that tivozanib, a pan-inhibitor of vascular endothelial growth factor (VEGF) receptors, inhibited proliferation of GBM cells through a G2/M cell cycle arrest via inhibition of polo-like kinase 1 (PLK1) signalling pathway and down-modulation of Aurora kinases A and B, cyclin B1 and CDC25C. Moreover, tivozanib decreased adhesive potential of these cells through reduction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Tivozanib diminished GBM cell invasion through impairing the proteolytic cascade of cathepsin B/urokinase-type plasminogen activator (uPA)/matrix metalloproteinase-2 (MMP-2). Combination of tivozanib with EGFR small molecule inhibitor gefitinib synergistically increased sensitivity to gefitinib. Altogether, these findings suggest that VEGFR blockade by tivozanib has potential anti-glioma effects in vitro. Further in vivo studies are warranted to explore the anti-tumour activity of tivozanib in combinatorial approaches in GBM.

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“…Emerging data indicate that the VEGF ligands act as survival factors for tumour cells that express the receptors545556. In colorectal cancer cells, VEGFA depletion reduces cell survival and enhances chemosensitivity via blockade of AKT and ERK1/2 pathways57.…”

Section: Discussionmentioning

confidence: 99%

Anti-tumour activity of tivozanib, a pan-inhibitor of VEGF receptors, in therapy-resistant ovarian carcinoma cells

Momeny

Sabourinejad

Zarrinrad

et al. 2017

Sci Rep

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Epithelial ovarian cancer (EOC) is the most fatal gynaecological malignancy. Despite initial therapeutic response, the majority of advanced-stage patients relapse and succumb to chemoresistant disease. Overcoming drug resistance is the key to successful treatment of EOC. Members of vascular endothelial growth factor (VEGF) family are overexpressed in EOC and play key roles in its malignant progression though their contribution in development of the chemoresistant disease remains elusive. Here we show that expression of the VEGF family is higher in therapy-resistant EOC cells compared to sensitive ones. Overexpression of VEGFR2 correlated with resistance to cisplatin and combination with VEGFR2-inhibitor apatinib synergistically increased cisplatin sensitivity. Tivozanib, a pan-inhibitor of VEGF receptors, reduced proliferation of the chemoresistant EOC cells through induction of G2/M cell cycle arrest and apoptotic cell death. Tivozanib decreased invasive potential of these cells, concomitant with reduction of intercellular adhesion molecule-1 (ICAM-1) and diminishing the enzymatic activity of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-2 (MMP-2). Moreover, tivozanib synergistically enhanced anti-tumour effects of EGFR-directed therapies including erlotinib. These findings suggest that the VEGF pathway has potential as a therapeutic target in therapy-resistant EOC and VEGFR blockade by tivozanib may yield stronger anti-tumour efficacy and circumvent resistance to EGFR-directed therapies.

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Vascular endothelial growth factor-C modulates proliferation and chemoresistance in acute myeloid leukemic cells through an endothelin-1-dependent induction of cyclooxygenase-2

Cited by 23 publications

References 45 publications

Functions of endothelin-1 in apoptosis and migration in hepatocellular carcinoma

Functions of endothelin-1 in apoptosis and migration in hepatocellular carcinoma

Blockade of vascular endothelial growth factor receptors by tivozanib has potential anti-tumour effects on human glioblastoma cells

Anti-tumour activity of tivozanib, a pan-inhibitor of VEGF receptors, in therapy-resistant ovarian carcinoma cells

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