scholarly journals Antitumor Efficacy and Mechanism in Hepatoma H22-Bearing Mice ofBrucea javanicaOil

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Wen-Rong Shi ◽  
Yan Liu ◽  
Xiao-Ting Wang ◽  
Qiong-Ying Huang ◽  
Xue-Rong Cai ◽  
...  

Brucea javanicais a traditional herbal medicine in China, and its antitumor activities are of research interest.Brucea javanicaoil, extracted with ether and refined with 10% ethyl alcohol fromBrucea javanicaseed, was used to treat hepatoma H22-bearing mice in this study. The antitumor effect and probable mechanisms of the extractedBrucea javanicaoil were studied in H22-bearing mice by WBC count, GOT, GPT levels, and western blotting. The H22 tumor inhibition ratio of 0.5, 1, and 1.5 g/kg bwBrucea javanicaoil were 15.64%, 23.87%, and 38.27%.Brucea javanicaoil could inhibit the involution of thymus induced by H22 tumor-bearing, but it could not inhibit the augmentation of spleen and liver.Brucea javanicaoil could decrease the levels of WBC count and GOT and GPT in H22-bearing mice. The protein levels of GAPDH, Akt, TGF-β1, andα-SMA in tumor tissues decreased after being treated withBrucea javanicaoil. Disturbing energy metabolism and neoplastic hyperplasia controlled by Akt and immunoregulation activity were its probable antitumor mechanisms in hepatoma H22-bearing mice.

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Hanzhang Zhu ◽  
Weijiang Zhou ◽  
Yafeng Wan ◽  
Ke Ge ◽  
Jun Lu ◽  
...  

Abstract Background The present study aims to develop a nanoparticle encapsulating doxorubicin (DOX) and programmed death-ligand 1 (PD-L1) siRNA and evaluate its anti-tumor effects on hepatoma carcinoma (HCC). Methods Nanoparticle encapsulating DOX and PD-L1 siRNA (NPDOX/siPD-L1) was characterized by dynamic light scattering and transmission electron microscopy. Flow cytometry was applied to analyze cell populations, NPDOX/siPD-L1 internalization, and cell apoptosis. Real-Time (RT)-quantitative reverse transcription (qPCR) and western blotting were used to determine the mRNA and protein levels, respectively. Released ATP was determined using ATP determination kit and cytokines were determined using specific ELISAs. A tumor-bearing animal model was established to evaluate the anti-tumor effects of NPDOX/siPD-L1. Results Treatment of NPDOX/siPD-L1 induced immunogenic cell death (ICD) and PD-L1 overexpression in HCC. In vivo study demonstrated that intravenously injection of NPDOX/siPD-L1 significantly inhibited the tumor volume and PD-L1 expressions of tumor tissue in the H22 tumor-bearing animal model. Besides, the treatment of NPDOX/siPD-L1 also regulated the populations of matured dendritic cells and cytotoxic T cells and the productions of cytokines in the tumor tissues. Conclusion Taken together, NPDOX/siPD-L1 showed significant anti-tumor effects on HCC by the induction of ICD and inhibition of PD-L1 overexpression.


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Katsuya Ohbuchi ◽  
Shin Nishiumi ◽  
Naoki Fujitsuka ◽  
Tomohisa Hattori ◽  
Masahiro Yamamoto ◽  
...  

Cancer cachexia, which is characterized by decreased food intake, weight loss and systemic inflammation, increases patient’s morbidity and mortality. We previously showed that rikkunshito (RKT), a Japanese traditional herbal medicine (Kampo), ameliorated the symptoms of cancer cachexia through ghrelin signaling-dependent and independent pathways. To investigate other mechanisms of RKT action in cancer cachexia, we performed metabolome analysis of plasma in a rat model bearing the Yoshida AH-130 hepatoma. A total of 110 metabolites were detected in plasma and RKT treatment significantly altered levels of 23 of those metabolites in cachexia model rats. Among them, glucarate, which is known to have anticarcinogenic activity through detoxification of carcinogens via inhibition ofβ-glucuronidase, was increased in plasma following administration of RKT. In our AH-130 ascites-induced cachexia rat model, administration of glucarate delayed onset of weight loss, improved muscle atrophy, and reduced ascites content. Additionally, glucarate reduced levels of plasma interferon-γ(IFN-γ) in tumor-bearing rats and was also found to suppress LPS-induced IFN-γexpression in splenocytesin vitro. These results suggest that glucarate has anti-inflammatory activity via a direct effect on immune host cells and suggest that RKT may also ameliorate inflammation partly through the elevation of glucarate in plasma.


Author(s):  
Weiming Yang ◽  
Weiheng Zhang ◽  
Xiaozhong Wang ◽  
Liming Tan ◽  
Hua Li ◽  
...  

Background: The antigen HCA587 (also known as MAGE-C2), which is considered a cancer-testis antigen, exhibits upregulated expression in a wide range of malignant tumors with unique immunological properties, and may thus serve as a promising target for tumor immunotherapy. Objective: To explore the antitumor effect of the HCA587 protein vaccine and the response of humoral and cell-mediated immunity. Methods: The HCA587 protein vaccine was formulated with adjuvants CpG and and ISCOM. B16 melanoma cells were subcutaneously inoculated to C57BL/6 mice, followed by treatment with HCA587 protein vaccine subcutaneously. Mouse survival was monitored daily, and tumor volume was measured every 2 to 3 days. The tumor sizes, survival time and immune cells in tumor tissues were detected. And the vital immune cell subset and effector molecules were explored. Results: After treatment with HCA587 protein vaccine, the vaccination generated elicited significant immune responses, which delayed tumor growth and improved animal survival. The vaccination increased the proportion of CD4+ T cells expressing IFN-γ and granzyme B in tumor tissues. Depletion of CD4+T cells resulted in an almost complete abrogation of the antitumor effect of the vaccination, suggesting that the antitumor efficacy was mediated by CD4+ T cells. In addition, knockout of IFN-γ resulted in a decrease in granzyme B levels which were secreted by CD4+ T cells, and the antitumor effect was also significantly attenuated. Conclusion: The HCA587 protein vaccine may increase the levels of granzyme B expressed by CD4+ T cells, and this increase is dependent on IFN-γ, and the vaccine resulted in a specific tumor immune response and subsequent eradication of the tumor.


Life Sciences ◽  
2003 ◽  
Vol 73 (21) ◽  
pp. 2687-2701 ◽  
Author(s):  
Bolin Qin ◽  
Masaru Nagasaki ◽  
Ming Ren ◽  
Gustavo Bajotto ◽  
Yoshiharu Oshida ◽  
...  

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