scholarly journals Shenqi Fuzheng Injection (SFI) Enhances IFN-α Inhibitory Effect on Hepatocellular Carcinoma Cells by Reducing VEGF Expression: Validation by Gene Silencing Technique

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Xiaoheng Chen ◽  
Shuo Qi ◽  
Zhe Li ◽  
Bei He ◽  
Hui long Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mtt Assay ◽  
Synergistic Effects ◽  
Inhibitory Effect ◽  
Vascular Endothelial ◽  
Vegf Gene ◽  
Anticancer Properties ◽  
L Cells ◽  
Shenqi Fuzheng Injection ◽  
Endothelial Growth Factor

Shenqi Fuzheng Injection (SFI) is a traditional Chinese medicine injection with anticancer properties and is mainly composed of ginseng and astragalus. Its efficacy has been confirmed in clinical trials, but the mechanism remains unclear. We investigated the effect of SFI on vascular endothelial growth factor (VEGF) gene expression in hepatocellular carcinoma (HCC) cells and identified its possible mechanism of synergistic effects when combined with the chemotherapeutic drug interferon (IFN-) α. An MTT assay was used to measure the inhibition effects of low-dose IFN-α (6000 IU) with or without SFI (0.5 g/L) on the HCC cell line MHCC97. VEGF-silenced MHCC97L-mir200 cell lines were prepared using lentiviral vectors and evaluated by real-time PCR to determine the inhibition effect. We examined MHCC97L-mir200 and MHCC97L cells by MTT assay, using IFN-α alone or in combination with SFI. The inhibition ratio of IFN-α (6000 IU) was -29.5%, while that for IFN-α (6000 IU) + SFI (0.5 g/L) was 17.0%, which was significantly higher than that for the IFN-α group (P < 0.01). The VEGF gene was silenced successfully in MHCC97-L cells. After interference of VEGF, the inhibition by SFI and IFN-α in MHCC97L-mir200 did not differ from that in MHCC97-L cells (P > 0.05). SFI can reduce the expression of VEGF in HCC, which can increase the efficacy of IFN-α, providing a theoretical basis for clinical application.

scholarly journals H2O2-responsive VEGF/NGF gene co-delivery nano-system achieves stable vascularization in ischemic hindlimbs

2021 ◽  
Author(s):  
Youlu Chen ◽  
Zuoguan Chen ◽  
Jianwei Duan ◽  
Liang Gui ◽  
Huiyang Li ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Growth Factor ◽  
Synergistic Effects ◽  
Single Gene ◽  
Blood Perfusion ◽  
Tube Formation ◽  
Vascular Endothelial ◽  
Mice Model ◽  
Vegf Gene ◽  
Endothelial Growth Factor

Abstract Peripheral vascular disease (PVD) is a common clinical manifestation of atherosclerosis. Vascular endothelial growth factor (VEGF) gene therapy is a promising approach for PVD treatment. However, due to single-gene therapy limitations and high H 2 O 2 pathological microenvironment, VEGF gene therapy are not as expectations and its clinical application are limited. Synergistic effects of Nerve factors and vascular factors in angiogenesis have attracted attention in recent years. In this study, VEGF and nerve growth factor (NGF) genes co-delivery nanoparticles (VEGF/NGF-NPs) were prepared by using H 2 O 2 responsive 6s-PLGA-Po-PEG as a carrier. 6s-PLGA-Po-PEG could react with H 2 O 2 specifically due to the internal peroxalate bond. Angiogenic effects of VEGF/NGF-NPs has been evaluated in cells and hindlimb ischemia mice model. Results showed that VEGF/NGF-NPs promoted VEGF and NGF co-expression simultaneously, eliminated excessive H 2 O 2 , strengthened reactions between SH-SY5Ys and HUVECs, and finally enhanced migration, tube formation, proliferation and H 2 O 2 damage resistance of HUVECs. VEGF/NGF-NPs also recovered blood perfusion, promoted the expression of VEGF, NGF, eNOS and NO, and enhanced vascular coverage of pericytes. Treatment effects of VEGF/NGF-NPs may related to VEGF/eNOS/NO pathway. Altogether, VEGF/NGF-NPs eliminated excessive H 2 O 2 while achieving gene co-delivery, and promoted stable angiogenesis. It’s a promising way for PVD treatment by using VEGF/NGF-NPs.

Synergistic Antitumor Effect of 5-Fluorouracil Combined with Constituents from Pleurospermum lindleyanum in Hepatocellular carcinoma SMMC-7721 Cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Xiao-Feng Zhu ◽  
Xiao-Jin Li ◽  
Zhong-Lian Cao ◽  
Xiu-Jie Liu ◽  
Ping Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Effectiveness ◽  
Synergistic Effects ◽  
Folk Medicine ◽  
Inhibitory Effect ◽  
Caspase 9 ◽  
Whole Plant ◽  
Anti Cancer ◽  
Induced Apoptosis

Background: A Chinese folk medicine plant Pleurospermum lindleyanum possesses pharmacological activities of heat-clearing, detoxifying and preventing from hepatopathy, coronary heart disease, hypertension, and high altitude sickness. We isolated and characterized its constituents to investigate its synergistic effects against human hepatoma SMMC-7721 cells. Objective: The aim of this study was to explore the synergistic anti-cancer activities of isolates from P. lindleyanum with 5-FU on hepatoma SMMC-7721 cells in vitro and their primary mechanisms. Methods: Sequential chromatographic techniques were conducted for the isolation studies. The isolates structures were established by spectroscopic analysis as well as X-ray crystallographic diffraction. Growth inhibition was detected by MTT assay. The isobologram method was used to assess the effect of drug combinations. Flow cytometry and western blot were used to examine apoptosis and protein expression. Results: A new coumarin (16), along with sixteen known compounds, were isolated from the whole plant of P. lindleyanum and their structures were elucidated by spectroscopic methods. Four coumarins (2, 3, 5, and 16), two flavonoids (8 and 9) and three phytosterols and triterpenes (12-14) were found to synergistically enhance the inhibitory effect of 5-FU against SMMC-7721 cells. Among them, compounds 3 and 16 exhibited the best synergistic effects with IC50 of 5-FU reduced by 16-fold and 22-fold possessing the minimum Combination Index (CI) 0.34 and 0.27. The mechanism of action of combinations might be through synergistic arresting for the cell cycle at G1 phases and the induction of apoptosis. Moreover, western blotting and molecular docking revealed that compounds 3 or 5 might promote 5-FU-induced apoptosis by regulating the expression of Caspase 9 and PARP. Conclusion: Constituents from P. lindleyanum may improve the treatment effectiveness of 5-FU against hepatocellular carcinoma cells.

Effect of co-treatment with doxorubicin and verapamil loaded into chitosan nanoparticles on diethylnitrosamine-induced hepatocellular carcinoma in mice

2020 ◽  
Vol 39 (11) ◽  
pp. 1528-1544 ◽  
Author(s):  
HE Abo Mansour ◽  
MM El-Batsh ◽  
NS Badawy ◽  
ET Mehanna ◽  
NM Mesbah ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Anticancer Activity ◽  
Hepg2 Cells ◽  
Chitosan Nanoparticles ◽  
B Cell Lymphoma ◽  
Favorable Effect ◽  
Vascular Endothelial ◽  
Factor Α ◽  
Endothelial Growth Factor

This study aimed to investigate the potential role of co-treatment with doxorubicin (DOX) and verapamil (VRP) nanoparticles in experimentally induced hepatocellular carcinoma in mice and to investigate the possible mechanisms behind the potential favorable effect of the co-treatment. DOX and VRP were loaded into chitosan nanoparticles (CHNPs), and cytotoxicity of loaded and unloaded drugs against HepG2 cells was evaluated. Male albino mice were divided into eight groups ( n = 15): (1) normal control, (2) diethylnitrosamine, (3) CHNPs, (4) free DOX, (5) CHNPs DOX, (6) free VRP, (7) CHNPs VRP, and (8) CHNPs DOX + CHNPs VRP. Either VRP or DOX loaded into CHNPs showed stronger growth inhibition of HepG2 cells than their free forms. DOX or VRP nanoparticles displayed pronounced anticancer activity in vivo through the decline of vascular endothelial growth factor and B cell lymphoma-2 contents in liver tissues, upregulation of antioxidant enzymes, and downregulation of multidrug resistance 1. Moreover, reduced cardiotoxicity was evident from decreased level of tumor necrosis factor-α and malondialdehyde in heart tissues coupled with decreased serum activity of creatine kinase-myocardial band and lactate dehydrogenase. Co-treatment with CHNPs DOX and CHNPs VRP showed superior results versus other treatments. Liver sections from the co-treatment group revealed the absence of necrosis, enhanced apoptosis, and nearly normal hepatic lobule architecture. Co-treatment with CHNPs DOX and CHNPs VRP revealed enhanced anticancer activity and decreased cardiotoxicity versus the corresponding free forms.

scholarly journals Perforation of the Small Intestine after Introduction of Lenvatinib in a Patient with Advanced Hepatocellular Carcinoma

2020 ◽  
Vol 14 (1) ◽  
pp. 63-69 ◽  
Author(s):  
Naomi Suzuki ◽  
Kazuto Tajiri ◽  
Yuka Futsukaichi ◽  
Shinichi Tanaka ◽  
Aiko Murayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Small Intestine ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Vegf Receptor ◽  
Advanced Hepatocellular Carcinoma ◽  
Vascular Endothelial ◽  
First Line ◽  
Endothelial Growth Factor ◽  
Line Standard

Lenvatinib is a first-line standard treatment for advanced hepatocellular carcinoma (HCC) with better anti-tumor effects than sorafenib, as shown by greater inhibition of the kinases of fibroblast growth factor receptor and vascular endothelial growth factor (VEGF) receptor. This report describes a patient with advanced HCC who experienced perforation of the small intestine 1 month after starting the treatment with lenvatinib. This patient likely had partial necrosis of a metastasis to the small intestine before starting lenvatinib treatment, with subsequent ischemic changes leading to perforation of the small intestine. Although metastasis of HCC to the small intestine is rare, patients with these metastases should be regarded as being at risk for perforation during lenvatinib treatment.

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