scholarly journals Inhibition of Tumor Growth of Human Hepatocellular Carcinoma HepG2 Cells in a Nude Mouse Xenograft Model by the Total Flavonoids fromArachniodes exilis

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Huimin Li ◽  
Dengzhao Jiang ◽  
Lei Zhang ◽  
Jiazhong Wu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Nude Mice ◽  
Hepg2 Cells ◽  
Xenograft Model ◽  
Human Hepatocellular Carcinoma ◽  
Total Flavonoids ◽  
Tumor Growth Model ◽  
Mouse Xenograft Model

A tumor growth model of human hepatocellular carcinoma HepG2 cells in nude mice was employed to investigate the antitumor activity of the total flavonoids extracted fromArachniodes exilis(TFAE)in vivo. Several biochemical assays including hematoxylin-eosin (HE) staining, immunohistochemistry, and Western blot were performed to elucidate the mechanism of action of total flavonoids extracted fromArachniodes exilis(TFAE). The results showed that TFAE effectively inhibited the tumor growth of hepatocellular carcinoma in nude mice and had no significant effect on body weight, blood system, and functions of liver and kidney. Expression levels of proapoptotic proteins Bax and cleaved caspase-3 remarkably increased while the expressions of Bcl-2, HIF-1α, and VEGF were suppressed by TFAE. These results suggested that the antitumor potential of TFEA was implied by the apoptosis of tumor cells and the inhibition of angiogenesis in tumor tissue.

scholarly journals Chinese Formula Ganji Fang Inhibits Tumor Growth Through Regulating Cell Mitosis by Reducing ARPP-19 Expression in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Chunlei Zhang ◽  
Kaiyue Tang ◽  
Lili Yang ◽  
Yang Liu ◽  
Yifan Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Survival Time ◽  
Nude Mice ◽  
Tumor Volume ◽  
Xenograft Model ◽  
The Body ◽  
Proliferation Index ◽  
Mouse Xenograft Model ◽  
Liver And Kidney

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies with high rate of mortality worldwide. Rare effective treatment is available for HCC patients especially at advanced stage. Ganji Fang (GJF), one formula of traditional Chinese medicine (TCM), has shown therapeutic effect on HCC in clinical application. This study aims at evaluating the anti-HCC effect and safety of GJF treatment, as well as exploring the potential underlying molecular mechanism by using HCC mouse model. Methods: HepG2 cells were subcutaneously injected into the upper flank of male BALB/c nude mice to establish the HCC Xenograft model. Mice were randomly assigned to three groups, treated respectively with high (GJF-H group) or low dose (GJF-L group) of GJF or vehicle (Control group) via gavage. The tumor volume was detected dynamically. Four weeks later, the weight and proliferation activity of tumors were measured. Western blot and immunohistochemistry were used to detect the expression of cAMP-regulated phosphoprotein 19 (ARPP-19) and the regulated molecules. H&E staining of tissue section of liver and kidney was used to assess the toxicity of the formula. Foe investigation of survival time, SMMC 7721 cells were injected subcutaneously to the BALB/c-nude mice. The tumor-bearing mice were allocated into two groups (Control and GJF-H) and treated as above description. The death number of mice was recorded and the survival time was analyzed.Results: Compared with control, the body weight and activity of GJF-treated mice were improved obviously. No toxic change was observed in tissues of liver and kidney. The tumor volume and weight was significantly down-regulated by GJF dose-dependently. The mice with GJF treatment showed the tendency of prolonging survival time. The proliferation index and PCNA expression in the tumor of GJF group were lower than in control. Furthermore, GJF down-regulated levels of ARPP-19 and phospho-(Ser) CDKs substrates, up-regulated level of inactivated cyclin division cycle 2 (Cdc2). Conclusion: GJF can effectively inhibit tumor growth of HCC and improve the general condition of the nude mouse xenograft model. The mechanism of inhibiting tumor growth is partially related to down-regulating ARPP-19 to inhibit mitosis and cell proliferation of HCC.

scholarly journals Establishment and characteristic of an orthotopic implantation model of human hepatocellular carcinoma with Luc-GFP-labeled in nude mice

2018 ◽  
Author(s):  
Jing-jing Zhang ◽  
Min-hua Xu ◽  
Jie Wang ◽  
Xiao-bao Jin ◽  
Yan Ma
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Suspension ◽  
Cell Line ◽  
Nude Mice ◽  
Xenograft Model ◽  
Human Hepatocellular Carcinoma ◽  
Orthotopic Model ◽  
Injection Method ◽  
Tumor Fragment

AbstractAimTo construct Luc-GFP-labeled human hepatocellular carcinoma (HCC) cell line with high metastatic potential. And to establish a spontaneous metastasis and conveniently monitored orthotopic model of hepatocellular carcinoma in nude mice. Methods: HCCLM3-Luc-GFP cell line stably expressing luciferase (Luc) and green fluorescent protein (GFP) was constructed by lentivirus transfection. The orthotopic xenograft model was established though cell suspension injection method and tumor fragment implanted method. The growth and metastasis of the tumors were observed by in vivo imaging and pathology. Results: HCCLM3-Luc-GFP, a highly metastatic HCC cell line with GFP expression and Luc activity, was obtained. The tumorigenic rates both of two approaches were 100%, but the lung metastatic rate was higher the former than the latter. Conclusion: The orthotopic model of highly metastatic and Luc-GFP-labeled HCC in nude mice was successfully established by above approaches, called as cell suspension injection method and tumor fragment implanted method, respectively. This study provides a new and effective means to monitor the growth of tumors in vivo and to evaluate the efficacy of anti-metastatic drugs against HCC.

scholarly journals LINC00680 enhances hepatocellular carcinoma stemness behavior and chemoresistance by sponging miR-568 to upregulate AKT3

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Gege Shu ◽  
Huizhao Su ◽  
Zhiqian Wang ◽  
Shihui Lai ◽  
Yan Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Mechanism Study ◽  
Downstream Signaling ◽  
Mouse Xenograft Model ◽  
High Level

Abstract Background Hepatocellular carcinoma (HCC) has an extremely poor prognosis due to the development of chemoresistance, coupled with inherently increased stemness properties. Long non-coding RNAs (LncRNAs) are key regulators for tumor cell stemness and chemosensitivity. Currently the relevance between LINC00680 and tumor progression was still largely unknown, with only one study showing its significance in glioblastoma. The study herein was aimed at identifying the role of LINC00680 in the regulation HCC stemness and chemosensitivity. Methods QRT-PCR was used to detect the expression of LINC00680, miR-568 and AKT3 in tissue specimen and cell lines. Gain- or loss-of function assays were applied to access the function of LINC00680 in HCC cells, including cell proliferation and stemness properties. HCC stemness and chemosensitivity were determined by sphere formation, cell viability and colony formation. Luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays were performed to examine the interaction between LINC00680 and miR-568 as well as that between miR-568 and AKT3. A nude mouse xenograft model was established for the in vivo study. Results We found that LINC00680 was remarkably upregulated in HCC tissues. Patients with high level of LINC00680 had poorer prognosis. LINC00680 overexpression significantly enhanced HCC cell stemness and decreased in vitro and in vivo chemosensitivity to 5-fluorouracil (5-Fu), whereas LINC00680 knockdown led to opposite results. Mechanism study revealed that LINC00680 regulated HCC stemness and chemosensitivity through sponging miR-568, thereby expediting the expression of AKT3, which further activated its downstream signaling molecules, including mTOR, elF4EBP1, and p70S6K. Conclusion LINC00680 promotes HCC stemness properties and decreases chemosensitivity through sponging miR-568 to activate AKT3, suggesting that LINC00680 might be a potentially important HCC diagnosis marker and therapeutic target.

scholarly journals MNAT1 promotes proliferation and the chemo-resistance of osteosarcoma cell to cisplatin through regulating PI3K/Akt/mTOR pathway

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Chensheng Qiu ◽  
Weiliang Su ◽  
Nana Shen ◽  
Xiaoying Qi ◽  
Xiaolin Wu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Xenograft Model ◽  
Mtor Pathway ◽  
Regulation Mechanism ◽  
Osteosarcoma Cell ◽  
Migration Ability ◽  
Mouse Xenograft Model

Abstract Background MNAT1 (menage a trois 1, MAT1), a cyclin-dependent kinase-activating kinase (CAK) complex, highly expressed in diverse cancers and was involved in cancer molecular pathogenesis. However, its deliverance profile and biological function in osteosarcoma (OS) remain unclear. Methods The expression of MNAT1 in OS was detected by western blot (WB) and immunohistochemistry (IHC). The potential relationship between MNAT1 molecular level expression and OS clinical expectations were analyzed according to tissues microarray (TMA). Proliferation potential of OS cells was evaluated in vitro based on CCK8 and OS cells colony formation assays, while OS cells transwell and in situ tissue source wound healing assays were employed to analyze the OS cells invasion and migration ability in vitro. A nude mouse xenograft model was used to detect tumor growth in vivo. In addition, ordinary bioinformatics analysis and experimental correlation verification were performed to investigate the underlying regulation mechanism of OS by MNAT1. Results In this research, we found and confirmed that MNAT1 was markedly over-expressed in OS tissue derived in situ, also, highly MNAT1 expression was closely associated with bad clinical expectations. Functional studies had shown that MNAT1 silencing could weaken the invasion, migration and proliferation of OS cells in vitro, and inhibit OS tumor growth in vivo. Mechanism study indicated that MNAT1 contributed to the progression of OS via the PI3K/Akt/mTOR pathway. We further verified that the MNAT1 was required in the regulation of OS chemo-sensitivity to cisplatin (DDP). Conclusions Taken together, the data of the present study demonstrate a novel molecular mechanism of MNAT1 involved in the formation of DDP resistance of OS cells.

scholarly journals PRSS8 is Downregulated and Suppresses Tumour Growth and Metastases in Hepatocellular Carcinoma

2016 ◽  
Vol 40 (3-4) ◽  
pp. 757-769 ◽  
Author(s):  
Li Zhang ◽  
Guozhan Jia ◽  
Binya Shi ◽  
Guanqun Ge ◽  
Hongbin Duan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Hepg2 Cells ◽  
Tumour Growth ◽  
Xenograft Model ◽  
Tumour Suppressor ◽  
Poor Overall Survival

Background: Protease serine 8 (PRSS8), a trypsin-like serine peptidase, has been shown to function as a tumour suppressor in various malignancies. The present study aimed to investigate the expression pattern, prognostic value and the biological role of PRSS8 in human hepatocellular carcinoma (HCC). Methods: PRSS8 expression in 106 HCC surgical specimens was examined by Real-time polymerase chain reaction (PCR) and immunohistochemistry, and its clinical significance was analysed. The role of PRSS8 in cell proliferation, apoptosis and invasion were examined in vitro and in vivo. Results: PRSS8 mRNA and protein expression were decreased in most HCC tumours from that in matched adjacent non-tumour tissues. Low intratumoral PRSS8 expression was significantly correlated with poor overall survival (OS) in patients with HCC (P = 0.001). PRSS8 expression was an independent prognostic factor for OS (hazard ratio [HR] = 1.704, P = 0.009). Furthermore, restoring PRSS8 expression in high metastatic HCCLM3 cells significantly inhibited cell proliferation and invasion. In contrast, silencing PRSS8 expression in non-metastatic HepG2 cells significantly enhanced cell growth and invasion. Moreover, our in vivo data revealed that attenuated PRSS8 expression in HepG2 cells greatly promoted tumour growth, while overexpression of PRSS8 remarkably inhibited tumour growth in an HCCLM3 xenograft model. Enhanced cell growth and invasion ability mediated by the loss of PRSS8 expression was associated with downregulation of PTEN, Bax and E-cadherin and an upregulation in Bcl-2, MMP9 and N-cadherin. Conclusions: Our data demonstrate that PRSS8 may serve as a tumour suppressor in HCC progression, and represent a valuable prognostic marker and potential therapeutic target for HCC.

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