Association between breast cancer cell migration and radiosensitivity in�vitro

Hou, Jing; Li, Leilei; Zhu, Haizhen; Chen, Huan; Wei, Na; Dai, Min; Ni, Qing; Guo, Xiaomao

doi:10.3892/ol.2019.11027

Cited by 4 publications

(3 citation statements)

References 34 publications

(34 reference statements)

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“…As FN1 is highly expressed in tumor vessels and mediates angiogenesis during tumorigenesis, it also plays important roles in cancer progression. It has been reported that FN1 is highly expressed in breast cancer ( 16 ), nasopharyngeal carcinoma ( 17 ), oral squamous cell carcinoma ( 11 ) and thyroid carcinoma ( 18 ), and plays a regulatory role in the major inflammatory cells present in the tumor microenvironment. In addition, FN1 expression is significantly upregulated in uterine leiomyoma and is associated with trophoblast invasion, uterine proliferation and adhesion function ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

Fibronectin 1 inhibits the apoptosis of human trophoblasts by activating the PI3K/Akt signaling pathway

Chen

Zhuang

et al. 2020

Int J Mol Med

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The excessive apoptosis of human trophoblasts can cause pregnancy-related diseases. It has been reported that fibronectin 1 (FN1) is closely associated with the invasion of human trophoblasts. The aim of the present study was to examine the effects of FN1 on the apoptosis of human trophoblasts and to investigate the underlying molecular mechanisms. It was found that FN1, a differentially expressed gene (DEG) in the GSE127170 dataset, was identified as the hub gene in a protein-protein interaction (PPI) network generated using the cytoHubba plug-in of Cytoscape software. The Metascape website was used to perform GO enrichment analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database was used to perform KEGG pathway analysis. Experimental analyses revealed that FN1 expression was downregulated in the chorionic villus tissues of patients diagnosed with and mice subjected to spontaneous abortion (SA). CCK-8 and flow cytometric assays revealed that the knockdown of FN1 decreased the viability and promoted the apoptosis of JEG-3 and BeWo cells. In vivo experiments demonstrated that the knockdown of FN1 promoted the apoptosis of trophoblasts in the chorionic villus tissues obtained from mice subjected to SA, whereas FN1 overexpression increased cell viability and inhibited cell apoptosis. The protein levels of cleaved caspase-3 and Bax were increased by the silencing of FN1 and decreased by FN1 overexpression. The protein expression levels of Bcl-2, proliferating cell nuclear antigen (PCNA) and Ki67 were decreased by the silencing of FN1; however, the overexpression of FN1 increased these levels. The results of western blot analysis revealed that the knockdown of FN1 inhibited the PI3K/Akt signaling pathway, while the overexpression of FN1 activated the PI3K/Akt signaling pathway. Consistently, the apoptosis-inhibiting effect of FN1 overexpression was reversed by a PI3K/Akt signaling pathway inhibitor, and the apoptosis-promoting effect of FN1 silencing was reversed by a PI3K/Akt signaling pathway activator. On the whole, the findings of the present study demonstrate that the inhibition of FN1 induces the apoptosis of JEG-3 and BeWo cells, and the overexpression of FN1 inhibits cell apoptosis by activating the PI3K/Akt signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Fibronectin 1 inhibits the apoptosis of human trophoblasts by activating the PI3K/Akt signaling pathway

Chen

Zhuang

et al. 2020

Int J Mol Med

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“… 27 A number of studies have shown that the development of EMT and CSCs following radiotherapy promotes the ability of breast cancer cells to acquire metastatic properties. 1 , 28 , 29 , 30 This mechanism was recognized as a limitation of single radiation therapy 31 , and the need for a new treatment strategy to prevent metastasis and recurrence was emphasized. Small molecules inhibiting TGF-β/ALK5 kinase, vactosertib effectively inhibited lung metastasis from breast cancer in a mouse model and has been investigated in various ongoing clinical trials with cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Co-treatment with vactosertib, a novel, orally bioavailable activin receptor-like kinase 5 inhibitor, suppresses radiotherapy-induced epithelial-to-mesenchymal transition, cancer cell stemness, and lung metastasis of breast cancer

Choi

Park

Cho

et al. 2022

Radiology and Oncology

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Background Acquired metastasis and invasion of cancer cells during radiotherapy are in part due to induction of epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) properties, which are mediated by TGF-β signaling. Here we evaluated the anti-metastatic therapeutic potential of vactosertib, an orally bioavailable TGF-β type I receptor (activin receptor-like kinase 5, ALK5) inhibitor, via suppression of radiation-induced EMT and CSC properties, oxidative stress generation, and breast to lung metastasis in a breast cancer mouse model and breast cancer cell lines. Materials and methods Co-treatment of vactosertib with radiation was investigated in the 4T1-Luc allografted BALB/c syngeneic mouse model and in 4T1-Luc and MDA-MB-231 cells. The anti-metastatic therapeutic potential of vactosertib in breast cancer was investigated using fluorescence immunohistochemistry, real-time quantitative reverse transcription-polymerase chain reaction, western blotting, wound healing assay, mammosphere formation assay, and lung metastasis analysis in vitro and in vivo. Results Radiation induced TGF-β signaling, EMT markers (Vimentin, Fibronectin, Snail, Slug, Twist, and N-cadherin), CSC properties (expression of pluripotent stem cell regulators, mammosphere forming ability), reactive oxygen species markers (NOX4, 4-HNE), and motility of breast cancer cells in vitro and in vivo. Vactosertib attenuated the radiation-induced EMT and CSC properties by inhibiting ROS stress in breast cancer. Moreover, vactosertib combined with radiation showed a significant anti-metastatic effect with suppression of breast to lung metastasis in vivo. Conclusions These results indicate that inhibition of TGF-β signaling with vactosertib in breast cancer patients undergoing radiotherapy would be an attractive strategy for the prevention of cancer metastasis and recurrence.

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“…The most simplistic model of in vitro cancer research is a two-dimensional (2D) monolayer culture of cancer cell lines, which, in spite of being the most utilized model, cannot provide realistic data about the heterogeneous, multicellular tumor microenvironment (TME) in the body. Currently, various models such as animals [2,3], transwells [4], spheroids [5][6][7][8], organoids [8][9][10], and xenografts [11,12] are utilized in cancer research with many advantages and disadvantages [13,14]. Hence, there is a need to develop models that can be utilized for monitoring cell growth, viability, polarization, and differentiation, as well as for and studying migration and invasion of tumor cells into the surrounding TME.…”

Section: Introductionmentioning

confidence: 99%

3D Modeling of Epithelial Tumors—The Synergy between Materials Engineering, 3D Bioprinting, High-Content Imaging, and Nanotechnology

Trivedi

et al. 2021

IJMS

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The current statistics on cancer show that 90% of all human cancers originate from epithelial cells. Breast and prostate cancer are examples of common tumors of epithelial origin that would benefit from improved drug treatment strategies. About 90% of preclinically approved drugs fail in clinical trials, partially due to the use of too simplified in vitro models and a lack of mimicking the tumor microenvironment in drug efficacy testing. This review focuses on the origin and mechanism of epithelial cancers, followed by experimental models designed to recapitulate the epithelial cancer structure and microenvironment, such as 2D and 3D cell culture models and animal models. A specific focus is put on novel technologies for cell culture of spheroids, organoids, and 3D-printed tissue-like models utilizing biomaterials of natural or synthetic origins. Further emphasis is laid on high-content imaging technologies that are used in the field to visualize in vitro models and their morphology. The associated technological advancements and challenges are also discussed. Finally, the review gives an insight into the potential of exploiting nanotechnological approaches in epithelial cancer research both as tools in tumor modeling and how they can be utilized for the development of nanotherapeutics.

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Association between breast cancer cell migration and radiosensitivity in�vitro

Cited by 4 publications

References 34 publications

Fibronectin 1 inhibits the apoptosis of human trophoblasts by activating the PI3K/Akt signaling pathway

Fibronectin 1 inhibits the apoptosis of human trophoblasts by activating the PI3K/Akt signaling pathway

Co-treatment with vactosertib, a novel, orally bioavailable activin receptor-like kinase 5 inhibitor, suppresses radiotherapy-induced epithelial-to-mesenchymal transition, cancer cell stemness, and lung metastasis of breast cancer

3D Modeling of Epithelial Tumors—The Synergy between Materials Engineering, 3D Bioprinting, High-Content Imaging, and Nanotechnology

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