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.

miR-29a overexpresion induces apoptosis through targeting VEGF in hepatocellular carcinoma

2020 ◽  
Author(s):  
An-ji Wang ◽  
Hua-jun Wu ◽  
Chun-hui Yuan ◽  
Ke Ning ◽  
Huan-huan Hu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Myeloid Cell ◽  
B Cell Lymphoma ◽  
Cell Counting ◽  
Luciferase Assay ◽  
Vascular Endothelial ◽  
Dual Luciferase Assay ◽  
Proliferation And Apoptosis ◽  
Endothelial Growth Factor ◽  
Hcc Cells

Abstract Background : This study aimed to explore the role of miR-29a in hepatocellular carcinoma (HCC) cells. Further, to confirm whether miR-29a targetes vascular endothelial growth factor (VEGF) in HCC cells. Methods: Cell counting Kit-8 (CCK8) and clone formation assay were used to analyze the proliferation of HCC cells. Flow cytometry was performed to analyze the apoptosis and cell cycle of HCC cells. Western blot was used to analyze the expression of Bax, B-cell lymphoma-2 (Bcl-2), cyclin dependent kinase 4 (CDK4), CyclinD1, Retinoblastoma (Rb), p53 and myeloid cell leukemia-1 (MCL1). The targeting relations between miR-29a and VEGF was measuered by dual luciferase assay. Results : Overexpression of miR-29a could distinctly inhibit the proliferation and promote apoptosis of HCC cells. Overexpression of miR-29a obviously up-regulated the expressions of Bax and Rb, and reduced the expressions of CDK4, Bcl-2, Cyclin D1, p53, MCL1 and VEGF in HCC cells. Dual luciferase assay proved that VEGF was the target of miR-29a. Rescue experiments showed that miR-29a targeted VEGF to regulate the proliferation and apoptosis in HCC cells. Conclusions : These results indicated overexpression of miR-29a inhibited the HCC cells proliferation through targeting VEGF.

scholarly journals Total Saponin from Root ofActinidia valvataDunn Inhibits Hepatoma 22 Growth and MetastasisIn Vivoby Suppression Angiogenesis

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Guo-Yin Zheng ◽  
Hai-Liang Xin ◽  
Yan-Fen Xu ◽  
Bai Li ◽  
Xiao-Feng Zhai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Fibroblast Growth ◽  
Control Groups ◽  
Total Saponin ◽  
And Control ◽  
Endothelial Growth Factor

The root ofActinidia valvatadunn has been widely used in the treatment of hepatocellular carcinoma (HCC), proved to be beneficial for a longer and better life in China. In present work, total saponin from root ofActinidia valvataDunn (TSAVD) was extracted, and its effects on hepatoma H22-based mousein vivowere observed. Primarily transplanted hypodermal hepatoma H22-based mice were used to observe TSAVD effect on tumor growth. The microvessel density (MVD), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) are characterized factors of angiogenesis, which were compared between TSAVD-treated and control groups. Antimetastasis effect on experimental pulmonary metastasis hepatoma mice was also observed in the study. The results demonstrated that TSAVD can effectively inhibit HCC growth and metastasisin vivo, inhibit the formation of microvessel, downregulate expressions of VEGF and bFGF, and retrain angiogenesis of hepatoma 22 which could be one of the reasons.

The Antitumor Effects of Britanin on Hepatocellular Carcinoma Cells and its Real-Time Evaluation by In Vivo Bioluminescence Imaging

2020 ◽  
Vol 20 (9) ◽  
pp. 1147-1156
Author(s):  
Hanrui Li ◽  
GeTao Du ◽  
Lu Yang ◽  
Liaojun Pang ◽  
Yonghua Zhan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Western Blot ◽  
Blot Analysis ◽  
Tumor Size ◽  
Hepg2 Cells ◽  
Western Blot Analysis ◽  
Bioluminescence Imaging ◽  
Antitumor Effects ◽  
In Vivo Bioluminescence Imaging

Background: Hepatocellular carcinoma is cancer with many new cases and the highest mortality rate. Chemotherapy is the most commonly used method for the clinical treatment of hepatocellular carcinoma. Natural products have become clinically important chemotherapeutic drugs due to their great potential for pharmacological development. Many sesquiterpene lactone compounds have been proven to have antitumor effects on hepatocellular carcinoma. Objective: Britanin is a sesquiterpene lactone compound that can be considered for the treatment of hepatocellular carcinoma. The present study aimed to investigate the antitumor effect of britanin. Methods: BEL 7402 and HepG2 cells were used to study the cytotoxicity and antitumor effects of britanin. Preliminary studies on the nuclear factor kappa B pathway were conducted by western blot analysis. A BEL 7402-luc subcutaneous tumor model was established for the in vivo antitumor studies of britanin. In vivo bioluminescence imaging was conducted to monitor changes in tumor size. Results: The results of the cytotoxicity analysis showed that the IC50 values for britanin in BEL 7402 and HepG2 cells were 2.702μM and 6.006μM, respectively. The results of the colony formation demonstrated that the number of cells in a colony was reduced significantly after britanin treatment. And the results of transwell migration assays showed that the migration ability of tumor cells was significantly weakened after treatment with britanin. Tumor size measurements and staining results showed that tumor size was inhibited after britanin treatment. The western blot analysis results showed the inhibition of p65 protein expression and reduced the ratio of Bcl-2/Bax after treatment. Conclusion: A series of in vitro and in vivo experiments demonstrated that britanin had good antitumor effects and provided an option for hepatocellular carcinoma treatment.

Anticancer Activity of Platinum (II) Complex with 2-Benzoylpyridine by Induction of DNA Damage, S-Phase Arrest, and Apoptosis

2020 ◽  
Vol 20 (4) ◽  
pp. 504-517
Author(s):  
Yu-Lan Li ◽  
Xin-Li Gan ◽  
Rong-Ping Zhu ◽  
Xuehong Wang ◽  
Duan-Fang Liao ◽  
...  
Keyword(s):  
Dna Damage ◽  
B Cell ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Hepg2 Cells ◽  
Caspase 3 ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
S Phase ◽  
Caspase 9

Objective: To overcome the disadvantages of cisplatin, numerous platinum (Pt) complexes have been prepared. However, the anticancer activity and mechanism of Pt(II) complexed with 2-benzoylpyridine [Pt(II)- Bpy]: [PtCl2(DMSO)L] (DMSO = dimethyl sulfoxide, L = 2-benzoylpyridine) in cancer cells remain unknown. Methods: Pt(II)-Bpy was synthesized and characterized by spectrum analysis. Its anticancer activity and underlying mechanisms were demonstrated at the cellular, molecular, and in vivo levels. Results: Pt(II)-Bpy inhibited tumor cell growth, especially HepG2 human liver cancer cells, with a halfmaximal inhibitory concentration of 9.8±0.5μM, but with low toxicity in HL-7702 normal liver cells. Pt(II)- Bpy induced DNA damage, which was demonstrated through a marked increase in the expression of cleavedpoly (ADP ribose) polymerase (PARP) and gamma-H2A histone family member X and a decrease in PARP expression. The interaction of Pt(II)-Bpy with DNA at the molecular level was most likely through an intercalation mechanism, which might be evidence of DNA damage. Pt(II)-Bpy initiated cell cycle arrest at the S phase in HepG2 cells. It also caused severe loss of the mitochondrial membrane potential; a decrease in the expression of caspase-9 and caspase-3; an increase in reactive oxygen species levels; the release of cytochrome c and apoptotic protease activation factor; and the activation of caspase-9 and caspase-3 in HepG2 cells, which in turn resulted in apoptosis. Meanwhile, changes in p53 and related proteins were observed including the upregulation of p53, the phosphorylation of p53, p21, B-cell lymphoma-2-associated X protein, and NOXA; and the downregulation of B-cell lymphoma 2. Moreover, Pt(II)-Bpy displayed marked inhibitory effects on tumor growth in the HepG2 nude mouse model. Conclusion: Pt(II)-Bpy is a potential candidate for cancer chemotherapy.

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