scholarly journals Novel Bradykinin Receptor Inhibitors Inhibit Proliferation and Promote the Apoptosis of Hepatocellular Carcinoma Cells by Inhibiting the ERK Pathway

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3915
Author(s):  
Yiou Wang ◽  
Bingxue Zhang ◽  
Yibing Huang ◽  
Wenjun Yao ◽  
Fei Tao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Liver Cancer ◽  
Carcinoma Cells ◽  
Receptor Expression ◽  
The Novel ◽  
Protein Levels ◽  
B1 Receptor ◽  
Common Cancer ◽  
Induced Apoptosis

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Studies have shown that bradykinin (BK) is highly expressed in liver cancer. We designed the novel BK receptor inhibitors J051-71 and J051-105, which reduced the viability of liver cancer cells and inhibited the formation of cancer cell colonies. J051-71 and J051-105 reduced cell proliferation and induced apoptosis in HepG2 and BEL-7402 cells, which may be due to the inhibition of the extracellular regulated protein kinase (ERK) signaling pathway. In addition, these BK receptor inhibitors reversed the cell proliferation induced by BK in HepG2 and BEL-7402 cells by downregulating B1 receptor expression. Inhibiting B1 receptor expression decreased the protein levels of p-ERK and reduced the malignant progression of HCC, providing a potential target for HCC therapy.

scholarly journals Effects of miR-489 targeting on SOX4 gene on proliferation and apoptosis of human hepatocellular carcinoma cells

2020 ◽  
Vol 20 (3) ◽  
pp. 1292-1298
Author(s):  
Bing Wang ◽  
Wang-Xun Jin ◽  
Yun-Li Zhang ◽  
Ling Huang ◽  
Hai-Bin Ni ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Flow Cytometry ◽  
Cell Proliferation ◽  
Liver Cancer ◽  
Hepg2 Cells ◽  
Carcinoma Cells ◽  
Human Hepatocellular Carcinoma ◽  
Hepatocellular Carcinoma Cells ◽  
Human Hepatocellular Carcinoma Cells

Background: Hepatocellular carcinoma is one of the most common malignant tumors found all over the globe. Despite advances in surgery and chemotherapy, the five-year survival rate of patients with hepatocellular carcinoma is still low. It is known that the proliferation of hepatocellular carcinoma cells is closely related to the occurrence, development and prog- nosis of hepatocellular carcinoma. The present work investigates the expression of microRNA-489 (miR-489) in human hepatocellular carcinoma cells and its effect on the biological behavior of human hepatocellular carcinoma cells. Methods: The expression of miR-489 by fluorescence quantitative PCR detection in 30 patients with hepatoblastoma of liver cancer tissues and adjacent tissues was studied. Also, the determination of hepatoblastoma in four cell lines with differ- ent metastatic potential (HR8348, HCT116, HT29 and HEPG2) and the expression of miR-489 during miR-489 simulation process was studied. MTT assay, flow cytometry and Western blot analysis were performed to know the cell proliferation to detect the changes in cell cycle, apoptosis of cells, and SOX4 gene expression respectively. Results: RT-PCR results showed that the cells compared with pre-cancerous tissue, the expression level of miR-489 in hepatocellular carcinoma tissues than in adjacent tissue significantly decreased (P<0.05), and with liver cancer cell metastasis increased (P<0.05); analogue transfection constructed miR-489 overexpressing HEPG2 cell line by microRNA. MTT results showed that miR-489 can inhibit the proliferation of HEPG2 cells, the differences were statistically significant (P<0.05); flow cytometry results showed that miR-489 mimics was transfected into HEPG2 cells at 48 hours had no significant effect on cell cycle distribution (P > 0.05); but miR-489 expression could induce apoptosis, compared with the control group, the apoptosis of miR-489 mimics was significantly increased and the difference was statistically significant (P < 0.05). Conclusion: In conclusion, miR-489 can significantly inhibit the occurrence and development of hepatocellular carcinoma cells. The mechanism may be down regulated by the expression of SOX4 and inhibit cell proliferation. Further this study showed that the tumor cells SOX4 gene as a regulatory factor target the genes of miR-489 in hepatocellular carcinoma. Keywords: Hepatocellular carcinoma; mircroRNA-489; SOX4; apoptosis.

Synergistic Effect of α-Solanine and Cisplatin Induces Apoptosis and Enhances Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells

2020 ◽  
Vol 19 (18) ◽  
pp. 2197-2210 ◽  
Author(s):  
Sherien M. El-Daly ◽  
Shaimaa A. Gouhar ◽  
Amira M. Gamal-Eldeen ◽  
Fatma F. Abdel Hamid ◽  
Magdi N. Ashour ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Synergistic Effect ◽  
Cell Cycle Arrest ◽  
Combination Treatment ◽  
Carcinoma Cells ◽  
Cell Growth Inhibition ◽  
Cycle Arrest ◽  
Induced Apoptosis ◽  
Human Hepatocellular Carcinoma Cells

Aim: The clinical application of cisplatin is limited by severe side effects associated with high applied doses. The synergistic effect of a combination treatment of a low dose of cisplatin with the natural alkaloid α-solanine on human hepatocellular carcinoma cells was evaluated. Methods: HepG2 cells were exposed to low doses of α-solanine and cisplatin, either independently or in combination. The efficiency of this treatment modality was evaluated by investigating cell growth inhibition, cell cycle arrest, and apoptosis enhancement. Results: α-solanine synergistically potentiated the effect of cisplatin on cell growth inhibition and significantly induced apoptosis. This synergistic effect was mediated by inducing cell cycle arrest at the G2/M phase, enhancing DNA fragmentation and increasing apoptosis through the activation of caspase 3/7 and/or elevating the expression of the death receptors DR4 and DR5. The induced apoptosis from this combination treatment was also mediated by reducing the expression of the anti-apoptotic mediators Bcl-2 and survivin, as well as by modulating the miR-21 expression. Conclusion: Our study provides strong evidence that a combination treatment of low doses of α-solanine and cisplatin exerts a synergistic anticancer effect and provides an effective treatment strategy against hepatocellular carcinoma.

scholarly journals MiR-489-3p inhibits cell proliferation, migration, and invasion, and induces apoptosis, by targeting the BDNF-mediated PI3K/AKT pathway in glioblastoma

2020 ◽  
Vol 15 (1) ◽  
pp. 274-283
Author(s):  
Bo Zheng ◽  
Tao Chen
Keyword(s):  
Cell Proliferation ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Bdnf Mrna ◽  
Protein Levels ◽  
Rna Immunoprecipitation ◽  
Underlying Mechanisms ◽  
Induced Apoptosis ◽  
Protein Cell

AbstractAmong astrocyte tumors, glioblastoma (GBM) is the most malignant glioma, highly aggressive and invasive, with extremely poor prognosis. Previous research has reported that microRNAs (miRNAs) participate in the progression of many cancers. Thus, this study aimed to explore the role and the underlying mechanisms of microRNA (miR)-489-3p in GBM progression. The expression of miR-489-3p and brain-derived neurotrophic factor (BDNF) mRNA was measured by quantitative real-time polymerase chain reaction. Western blot analysis was used to detect BDNF protein and the PI3K/AKT pathway-related protein. Cell proliferation, apoptosis, migration, and invasion were analyzed using CKK-8 assay, flow cytometry, and transwell assay, respectively. The interaction between BDNF and miR-489-3p was explored by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. MiR-489-3p was down-regulated and BDNF was up-regulated in GBM tissues and cells. MiR-489-3p re-expression or BDNF knockdown inhibited GBM cell proliferation, migration, and invasion, and promoted apoptosis. BDNF was a target of miR-489-3p, and BDNF up-regulation reversed the effects of miR-489-3p on GBM cells. The protein levels of p-AKT and p-PI3K were notably reduced in GBM cells by overexpression of miR-489-3p, but were rescued following BDNF up-regulation. Therefore, miR-489-3p inhibited proliferation, migration, and invasion, and induced apoptosis, by targeting the BDNF-mediated PI3K/AKT pathway in GBM, providing new strategies for clinical treatment of GBM.

scholarly journals Intracellular alpha-fetoprotein interferes with all-trans retinoic acid induced ATG7 expression and autophagy in hepatocellular carcinoma cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shanshan Wang ◽  
Rilu Feng ◽  
Ying Shi ◽  
Dexi Chen ◽  
Honglei Weng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retinoic Acid ◽  
Carcinoma Cells ◽  
Alpha Fetoprotein ◽  
Cell Counting ◽  
All Trans Retinoic Acid ◽  
Induced Apoptosis ◽  
Anti Tumor Activity ◽  
Retinoid Acid ◽  
Hcc Cells

AbstractRetinoic acid and retinoid acid receptor (RA-RAR) signaling exhibits suppressive functions in the progression of hepatocellular carcinoma (HCC) through multiple mechanisms. However, whether RA-RAR signaling induces autophagy that contributes its anti-tumor activity in HCC remains elusive. In the current study, the effects of RA-RAR pathway on autophagy were investigated in two HCC cell lines: alpha-fetoprotein (AFP) positive PLC/PRF/5 and AFP negative HLE cells. Cell autophagy was analyzed with western blot for detection of LC3 conversion and p62/SQSTM1 degradation while autophagy flux was assayed using the mRFP-GFP-LC3 reporter. Cell apoptosis and viability were analyzed by caspase-3 activity, TdT-mediated dUTP nick end labeling (TUNEL) assay, and Cell Counting Kit (CCK)-8, respectively. Chromatin immunoprecipitation (ChIP) was employed to detect the binding of RAR onto the promoter of autophagy-relevant 7 (ATG7), and co-immunoprecipitation (CoIP) was used to analyze the interaction of AFP and RAR. The results showed that ATRA dosage and time-dependently induced high levels of cell autophagy in both the PLC/PRF/5 and HLE cells, which was accompanied with up-regulation of ATG7. ChIP assay showed that RAR was able to bind to its responsive elements on ATG7 promoter. Impairment of ATG7 induction or blockade of autophagy with chloroquine aggravated ATRA induced apoptosis of HCC cells. Furthermore, intracellular AFP was able to complex with RAR in PLC/PRF/5 cells. Knockdown of AFP in PLC/PRF/5 cells augmented the up-regulation of ATG7 by ATRA while overexpression of AFP in HLE cells attenuated ATRA induced ATG7 expression and autophagy. Thus, ATRA induced ATG7 and autophagy participated in its cytotoxicity on HCC cells and AFP interfere with the induction of ATG7 and autophagy through forming complex with RAR.

Sign in / Sign up

Export Citation Format

Share Document