scholarly journals Melittin Inhibits Hypoxia-Induced Vasculogenic Mimicry Formation and Epithelial-Mesenchymal Transition through Suppression of HIF-1α/Akt Pathway in Liver Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Qunwei Chen ◽  
Wanfu Lin ◽  
Zifei Yin ◽  
Yong Zou ◽  
Shufang Liang ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Vasculogenic Mimicry ◽  
Tumor Model ◽  
Akt Pathway ◽  
Mrna Levels ◽  
Mesenchymal Transition ◽  
Liver Cancer Cells ◽  
Phosphorylated Akt

In this study, we investigated whether melittin could suppress hypoxia-induced vasculogenic mimicry (VM) formation in liver cancer and explored the underlying mechanisms. Melittin significantly inhibited the proliferation of liver cancer cells with or without CoCl2presence. Melittin also significantly inhibited CoCl2-induced migration, invasion, and VM formation of liver cancer cells. CoCl2treatment suppressed the expression of E-cadherin and elevated the expression of N-cadherin and Vimentin. Melittin reversed the changes in the protein and mRNA levels of these epithelial-mesenchymal transition (EMT) markers. CoCl2-induced accumulation of HIF-1αincreased the level of phosphorylated Akt and upregulated the expression of VEGF and MMP-2/9. Melittin decreased the HIF-1αlevel and thereby suppressed the levels of p-Akt, VEGF, and MMP-2/9. In addition, the inhibitor of PI3K/Akt also suppressed CoCl2-induced EMT and liver cancer cells migration, and the activator of Akt, SC-79, partly blocked the effect of melittin on CoCl2-induced EMT and liver cancer cells migration. In the xenograft tumor model in nude mice, melittin treatment significantly suppressed the tumor growth, VM formation, and HIF-1αexpression in the tumor. In conclusion, this study indicates melittin may inhibit hypoxia-induced VM formation and EMT in liver cancer through inhibiting HIF-1α/Akt pathway.

scholarly journals Effects of Pyrrole-Imidazole Polyamides Targeting Human TGF-β1 on the Malignant Phenotypes of Liver Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2883 ◽  
Author(s):  
Keiko Takagi ◽  
Yutaka Midorikawa ◽  
Tadatoshi Takayama ◽  
Hayato Abe ◽  
Kyoko Fujiwara ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Grade ◽  
Expression Level ◽  
Mrna Levels ◽  
Mesenchymal Transition ◽  
Liver Cancer Cells ◽  
Tgf Β1

Synthetic pyrrole-imidazole (PI) polyamides bind to the minor groove of double-helical DNA with high affinity and specificity, and inhibit the transcription of corresponding genes. In liver cancer, transforming growth factor (TGF)-β expression is correlated with tumor grade, and high-grade liver cancer tissues express epithelial-mesenchymal transition markers. TGF-β1 was reported to be involved in cancer development by transforming precancer cells to cancer stem cells (CSCs). This study aimed to evaluate the effects of TGF-β1-targeting PI polyamide on the growth of liver cancer cells and CSCs and their TGF-β1 expression. We analyzed TGF-β1 expression level after the administration of GB1101, a PI polyamide that targets human TGF-β1 promoter, and examined its effects on cell proliferation, invasiveness, and TGF-β1 mRNA expression level. GB1101 treatment dose-dependently decreased TGF-β1 mRNA levels in HepG2 and HLF cells, and inhibited HepG2 colony formation associated with downregulation of TGF-β1 mRNA. Although GB1101 did not substantially inhibit the proliferation of HepG2 cells compared to untreated control cells, GB1101 significantly suppressed the invasion of HLF cells, which displayed high expression of CD44, a marker for CSCs. Furthermore, GB1101 significantly inhibited HLF cell sphere formation by inhibiting TGF-β1 expression, in addition to suppressing the proliferation of HLE and HLF cells. Taken together, GB1101 reduced TGF-β1 expression in liver cancer cells and suppressed cell invasion; therefore, GB1101 is a novel candidate drug for the treatment of liver cancer.

scholarly journals P4HB modulates epithelial‑mesenchymal transition and the β‑catenin/Snail pathway influencing chemoresistance in liver cancer cells

2020 ◽  
Vol 20 (1) ◽  
pp. 257-265
Author(s):  
Xing Ma ◽  
Jiening Wang ◽  
Juhua Zhuang ◽  
Xiaokun Ma ◽  
Ni Zheng ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Liver Cancer Cells

Study of zinc oxide nanoparticles on epithelial-mesenchymal transition and toxicity of spontaneous monocyte-mediated cytotoxity-7721 cells

2021 ◽  
Vol 11 (6) ◽  
pp. 832-838
Author(s):  
Luoluo Wang ◽  
Yi Ruan ◽  
Xiang Wu ◽  
Xinhua Zhou
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Exposure Time ◽  
Zinc Oxide Nanoparticles ◽  
Epithelial Mesenchymal Transition ◽  
Oxide Nanoparticles ◽  
Zno Nanoparticle ◽  
Nanoparticle Concentration ◽  
Mesenchymal Transition ◽  
Liver Cancer Cells

To explore the method of studying zinc oxide nanoparticles on the epithelial-mesenchymal transition and toxicity of liver cancer SMMC-7721 cells. Human liver cancer SMMC-7721 cells is stored in 90% FBS+10% DMSO liquid nitrogen. ZnO suspension was prepared, cell viability was assessed using MTT assay, cell apoptosis was analyzed by flow cytometry, and EMT-related proteins were detected by western blotting. Results showed LDH activity increased continuously with the increase in ZnO nanoparticle concentration and exposure time (P < 0.001). Both ATP and SOD activities gradually decreased with the increase in ZnO nanoparticle concentration and exposure time (both P < 0.001). The MTT assay revealed that with the increase in ZnO dose, the proliferation of SMMC-7721 liver cancer cells decreased gradually (P < 0.001), and with the continuous increase in exposure time to ZnO nanoparticles, the reproductive viability of these cells also continued to decline (P < 0.001). The apoptosis rate of SMMC-7721 liver cancer cells increased with the increase in ZnO dose (P < 0.001). Flow cytometry results demonstrated that the apoptosis rate of SMMC-7721 liver cancer cells increased with the continuous prolongation of treatment time (P < 0.001). Western blotting experiments revealed that the concentrations of vimentin, Snail, N-cadherin, and Slugn proteins in SMMC-7721 cells increased significantly, whereas those of E-cadherin and ZO-1 decreased significantly, with the increase in ZnO dose (both P < 0.001). Therefore, ZnO nanoparticles can induce apoptosis of SMMC-7721 liver cancer cells, inhibit cell proliferation and EMT, and can be used as a new nanoparticle carrier for potential treatment of liver cancer.

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