Theoretical Considerations in Using Animal Models of Metastasis and Brief Methodology for In Vivo Colorectal Cancer Models in SCID and Nude Mice

Author(s):  
Sue A. Watson ◽  
Rajendra Kumari

2021 ◽  
Vol 8 (4) ◽  
pp. 59
Author(s):  
Elisabete Nascimento-Gonçalves ◽  
Bruno A.L. Mendes ◽  
Rita Silva-Reis ◽  
Ana I. Faustino-Rocha ◽  
Adelina Gama ◽  
...  

Colorectal cancer is one of the most common gastrointestinal malignancies in humans, affecting approximately 1.8 million people worldwide. This disease has a major social impact and high treatment costs. Animal models allow us to understand and follow the colon cancer progression; thus, in vivo studies are essential to improve and discover new ways of prevention and treatment. Dietary natural products have been under investigation for better and natural prevention, envisioning to show their potential. This manuscript intends to provide the readers a review of rodent colorectal cancer models available in the literature, highlighting their advantages and disadvantages, as well as their potential in the evaluation of several drugs and natural compounds’ effects on colorectal cancer.



2018 ◽  
Vol 51 (4) ◽  
pp. 1969-1981 ◽  
Author(s):  
Xiangyu Zhu ◽  
Si-ping Ma ◽  
Dongxiang Yang ◽  
Yanlong Liu ◽  
Yong-peng Wang ◽  
...  

Background/Aims: Deregulation of microRNAs (miRNAs) has been associated with a variety of cancers, including colorectal cancer (CRC). Here, we investigated anomalous miR-142-3p expression and its possible functional consequences in primary CRC samples. Methods: The expression of miR-142-3p was measured by quantitative RT-PCR in 116 primary CRC tissues and adjacent non-tumor tissues. The effect of miR-142-3p up- or down-regulation in CRC-derived cells was evaluated in vitro by cell viability and colony formation assays and in vivo by growth assays in xenografted nude mice. Results: Using quantitative RT-PCR, we found that miR-142-3p was down-regulated in 78.4 % (91/116) of the primary CRC tissues tested when compared to the adjacent non-tumor tissues. We also found that the miR-142-3p mimic reduced in vitro cell viability and colony formation by inducing cell cycle arrest in CRC-derived cells, and inhibited in vivo tumor cell growth in xenografted nude mice. Inversely, we found that the miR-142-3p inhibitor increased the viability and colony forming capacity of CRC-derived cells and tumor cell growth in xenografted nude mice. In addition, we identified CDK4 as a potential target of miR-142-3p by predictions and dual-luciferase reporter assays. Concordantly, we found that miR-142-3p mimics and inhibitors could decrease and increase CDK4 protein levels in CRC-derived cells, respectively. Conclusion: From our results we conclude that miR-142-3p may act as a tumor suppressor in CRC and may serve as a tool for miRNA-based CRC therapy.



2020 ◽  
Author(s):  
Qing Song ◽  
Liu Yang ◽  
Zhifen Han ◽  
Xinnan Wu ◽  
Ruixiao Li ◽  
...  

Abstract Background: Tanshinone IIA (Tan IIA) is a major active ingredient extracted from Salvia miltiorrhiza, which has been proved to inhibit metastasis of various cancers including colorectal cancer (CRC). However, the detailed mechanisms of Tan IIA against CRC metastasis are not well explored. Epithelial-to-mesenchymal transition (EMT) exerts an important regulatory role in CRC metastasis, and our previous mechanism studies demonstrated that β-arrestin1 could regulate CRC EMT partly through β-catenin signaling pathway. Therefore, in this work we investigated whether Tan IIA could regulate CRC EMT through β-arrestin1-mediated β-catenin signaling pathway in vivo and in vitro.Methods: The nude mice tail vein metastasis model was established to observe the effect of Tan IIA on CRC lung metastasis in vivo. The lung metastasis was evaluated by living animal imaging and hemaoxylin-eosin staining. The migratory ability of CRC cells in vitro were measured by transwell and wound healing assays. The protein expression and cellular localization of β-arrestin1 and β-catenin were characterized by immunofluorescence staining and western blot. The β-catenin signaling pathway related proteins and EMT associated proteins in CRC cells were detected by western blot and immunohistochemistry. Results: Our results showed that Tan IIA inhibited the lung metastases of CRC cells in vivo and extended the survival time of nude mice. In vitro, Tan IIA increased the expression of E-cadherin, decreased the secretion of Snail, N-cadherin and Vimentin, thus suppressed EMT and the migratory ability of CRC cells. Further study found the mechanism involving in Tan IIA regulating EMT and metastasis, referring to the suppression of β-arrestin1 expression, reduction of β-catenin nuclear localization, thereby the decreased activity of β-catenin signaling. Conclusion: Our data revealed a new mechanism of Tan IIA on the suppression of EMT and metastasis in CRC via β-arrestin1-mediated β-catenin signaling pathway, and provided support for Tan IIA as anti-metastatic agents in CRC.



RSC Advances ◽  
2017 ◽  
Vol 7 (50) ◽  
pp. 31588-31596 ◽  
Author(s):  
Yilin Gao ◽  
Xingjun Zhu ◽  
Yuwen Zhang ◽  
Xiaofeng Chen ◽  
Li Wang ◽  
...  

Cit-UCNPs after IP injection exhibited significantly different biological processes from those after IV injection. The passive-tumour targeting effectiveness of cit-UCNPs via the IP route was higher than that via the IV route.



Author(s):  
O Ogunlade ◽  
SP Johnson ◽  
E Zhang ◽  
V Rajkumar ◽  
RB Pedley ◽  
...  


2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Qing Hua ◽  
Zhirong Sun ◽  
Yi Liu ◽  
Xuefang Shen ◽  
Weiwei Zhao ◽  
...  

AbstractKallikrein-related peptidase 8 (KLK8) acts as an oncogene or anti-oncogene in various tumours, and the abnormal expression of KLK8 is involved in the carcinogenesis of several tumours. However, the role of KLK8 in colorectal cancer (CRC) and the underlying mechanism remain largely unclear. In this study, the carcinogenic effect of KLK8 was determined via CCK-8 and colony formation assays in vitro and a xenograft model in nude mice in vivo. The metastasis-promoting effect of KLK8 was investigated with transwell migration and invasion assays and wound-healing assay in vitro and a metastasis model in nude mice in vivo. Bioinformatics analyses and mechanistic experiments were conducted to elucidate the molecular mechanism. Herein, we reported that KLK8 had a promotive effect on the proliferation, migration and invasion of RKO and SW480 cells. Epithelial−mesenchymal transition (EMT) played an important role in the promotive effects of KLK8 on CRC. In addition, protease-activated receptor-1 (PAR-1) antagonist SCH79797 but not protease-activated receptor-2 (PAR-2) antagonist FSLLRY-NH2 attenuated the proliferation, migration and invasion of KLK8-upregulated RKO and SW480 cells. PAR-1 antagonist SCH79797 reduced the tumour volume of xenograft model and decreased the metastatic nodules in the livers of metastasis model. Furthermore, SCH79797 could reverse the positive impact of KLK8 on the EMT process in CRC both in vitro and in vivo. Taken together, these findings demonstrated for the first time that KLK8 promoted EMT and CRC progression, and this effect might be, at least partly mediated by PAR1-dependent pathway.



2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jing Sang ◽  
Ruixue Tang ◽  
Min Yang ◽  
Qing Sun

The purpose of this study was to investigate the effect of metformin or the combination of metformin and 5-FU on the growth and metastasis of colorectal cancer (CRC). For the in vitro experiments, HCT 116 and SW1463 cell lines were treated with metformin or the combination of metformin and 5-FU. Cell proliferation and invasion were analyzed by CCK-8, colony formation, and transwell assay, respectively. For the in vivo experiments, the CRC xenograft nude mice model was used to observe the effects of metformin or combined with 5-FU on tumor growth and metastasis. Metformin significantly inhibited the proliferation and invasion of HCT116 and SW1463 cells in vitro, which showed synergetic effects to 5-FU. In CRC xenograft nude mice, metformin alone and metformin combined with 5-FU treatment significantly inhibited tumor cell proliferation and tumor metastasis. In summary, metformin played an inhibitory role in the proliferation and metastasis of CRC and had a synergistic effect with 5-FU. Metformin may be a potentially effective anti-metastatic drug or an anticancer adjuvant agent for treating CRC.



Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 227
Author(s):  
Eileen Reidy ◽  
Niamh A. Leonard ◽  
Oliver Treacy ◽  
Aideen E. Ryan

Although there have been many advances in recent years for the treatment of colorectal cancer (CRC), it still remains the third most common cause of cancer-related deaths worldwide. Many patients with late stage CRC display resistance to multiple different therapeutics. An important aspect in developing effective therapeutics for CRC patients is understanding the interactions that take place in the tumor microenvironment (TME), as it has been shown to contribute to drug resistance in vivo. Much research over the past 100 years has focused on 2D monolayer cultures or in vivo studies, however, the efficacy in translating these to the clinic is very low. More recent studies are turning towards developing an effective 3D model of CRC that is clinically relevant, that can recapitulate the TME in vitro and bridge the gap between 2D cultures and in vivo studies, with the aim of reducing the use of animal models in the future. This review summarises the advantages and limitations of different 3D CRC models. It emphasizes how different 3D models may be optimised to study cellular and extracellular interactions that take place in the TME of CRC in an effort to allow the development of more translatable effective treatment options for patients.



SpringerPlus ◽  
2015 ◽  
Vol 4 (1) ◽  
Author(s):  
Jaime Tomé-Amat ◽  
Miriam Olombrada ◽  
Javier Ruiz-de-la-Herrán ◽  
Eduardo Pérez-Gómez ◽  
Clara Andradas ◽  
...  


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