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

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.

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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