In-vitro Pre-Treatment of Cancer Cells with TGF-β1: A Novel Approach of Tail Vein Lung Cancer Metastasis Mouse Model for Anti-Metastatic Studies

2019 ◽  
Vol 12 (4) ◽  
pp. 249-260 ◽  
Author(s):  
Ghulam Jilany Khan ◽  
Li Sun ◽  
Muhammad Abbas ◽  
Muhammad Naveed ◽  
Talha Jamshaid ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Model ◽  
Cancer Metastasis ◽  
Human Lung ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Lung Cancer Metastasis ◽  
Pre Treatment ◽  
Tgf Β1

Background: Aggressive behavior of tumor metastasis comes from certain mutations, changes in cellular metabolic and signaling pathways that are majorly altered by tumor microenvironment (TME), its other components and growth factors like transforming growth factor-β1 (TGF-β1) which is chiefly known for its epithelial to mesenchymal transformation (EMT). EMT is a critical step of metastasis cascade in actual human lung cancer scenario. Objective: Our present study is focused on unveiling the in-vivo metastatic behavior of TGF-β1 treated lung cancer cells that undergo EMT. Methods: The lung cancer epithelial A549 cells were treated in-vitro with TGF-β1 (3-5ng/ml for 72 h) for EMT. After confirming the transformation of cells by phenotype modifications, wound healing and cell migration assay and qRT-PCR analyses of EMT biomarkers including E. Cadherin, Vimentin, Snail, Slug, MMP2 and MMP9; those TGF-β1 modified cells were probed with fluorescent trackers and were injected into the tail vein of BALB/c nude mice for metastatic dissemination studies. Results: Our findings indicate that the distribution of TGF-β1 treated A549 cells as compared to W.T A549 towards lungs is less in terms of total relative fluorescent cluster count, however, the difference is insignificant (52±4, 60±5 respectively). Additionally, we show that TGF-β1 treated cells tend to metastasize almost 2, 3, 1.5, 2 and 1.7 times more than W.T towards liver, brain, ovaries, bones and adrenal gland, respectively, which is very much like human lung cancer metastasis. Conclusion: Conclusively, it is the first study ever reporting that a pre-treatment of cells with TGF-β1 for experimental lung cancer metastasis mouse model may portray a more precise approach for the development of potential therapeutic treatments. Additional pre-treatment studies with the application of other TME conditions like hypoxia and factors like NFκB, VEGF etc. may be a future prospect to develop a better understanding.

Extract from the Leaves of Toona sinensis Roemor Exerts Potent Antiproliferative Effect on Human Lung Cancer Cells

2002 ◽  
Vol 30 (02n03) ◽  
pp. 307-314 ◽  
Author(s):  
Hui-Chiu Chang ◽  
Wen-Chun Hung ◽  
Ming-Shyan Huang ◽  
Hseng-Kuang Hsu
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Human Lung ◽  
Apoptotic Cell ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Lung Fibroblasts ◽  
Human Lung Cancer ◽  
Toona Sinensis

Recent study indicated that the components of Toona sinensis Roemor have potent anti-inflammatory and analgesic effects. These components have also been reported to inhibit the growth of boils in vivo. In this study, we investigated the effect of crude extract from the leaves of Toona sinensis Roemor on the proliferation of A549 lung cancer cells. We found that the extract effectively blocked cell cycle progression by inhibiting the expression of cyclin D1 and E in A549 cells. Additionally, incubation of the extract led to activation of caspase-3-like proteases and apoptotic cell death. Conversely, the extract did not show any significant cytotoxic effect on primarily cultured human foreskin fibroblasts or MRC-5 human lung fibroblasts. Therefore, antiproliferative action of the extract is specific for tumor cells. Our results suggest that the components of Toona sinensis Roemor have potent anticancer effects in vitro and identification of the useful components in the extract may lead to the development of a novel class of anticancer drugs.

scholarly journals Deficiency of Functional Iron-Sulfur Domains in ABCE1 Inhibits the Proliferation and Migration of Lung Adenocarcinomas By Regulating the Biogenesis of Beta-Actin In Vitro

2017 ◽  
Vol 44 (2) ◽  
pp. 554-566 ◽  
Author(s):  
Qian Yu ◽  
Xu Han ◽  
Da-Li Tian
Keyword(s):  
Lung Cancer ◽  
Cancer Metastasis ◽  
A549 Cells ◽  
Metastatic Progression ◽  
Lung Cancer Metastasis ◽  
And Migration ◽  
Opposing Effects ◽  
Proliferation And Migration

Background/Aims: ATP-binding cassette transporter E1 (ABCE1), a unique ABC superfamily member that bears two Fe-S clusters, is essential for metastatic progression in lung cancer. Fe-S clusters within ABCE1 are crucial for ribosome dissociation and translation reinitiation; however, whether these clusters promote tumor proliferation and migration is unclear. Methods: The interaction between ABCE1 and β-actin was confirmed using GST pull-down. The lung adenocarcinoma (LUAD) cell line A549 was transduced with lentiviral packaging vectors overexpressing either wild-type ABCE1 or ABCE1 with Fe-S cluster deletions (ΔABCE1). The role of Fe-S clusters in the viability and migration of cancer cells was evaluated using clonogenic, MTT, Transwell and wound healing assays. Cytoskeletal rearrangement was determined using immunofluorescent techniques. Results: Fe-S clusters were the key domains in ABCE1 involved in binding to β-actin. The proliferative and migratory capacity increased in cells overexpressing ABCE1. However, the absence of Fe-S clusters reversed these effects. A549 cells overexpressing ABCE1 exhibited irregular morphology and increased levels of cytoskeletal polymerization as indicated by the immunofluorescence images. In contrast, cells expressing the Fe-S cluster deletion mutant presented opposing effects. Conclusion: These results demonstrate the indispensable role of Fe-S clusters when ABCE1 participates in the proliferation and migration of LUADs by interacting with β-actin. The Fe-S clusters of ABCE1 may be potential targets for the prevention of lung cancer metastasis.

Anti-Metastatic Effects of Lupeol via the Inhibition of MAPK/ERK Pathway in Lung Cancer

2020 ◽  
Vol 21 (2) ◽  
pp. 201-206 ◽  
Author(s):  
Mital Bhatt ◽  
Mitesh Patel ◽  
Mohd Adnan ◽  
Mandadi N. Reddy
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Cancer Metastasis ◽  
A549 Cells ◽  
Cancer Therapeutics ◽  
Enzyme Linked Immunosorbent Assay ◽  
Erk Pathway ◽  
Cytotoxic Effects ◽  
Lung Cancer Metastasis

Background and Objective: ERK pathway is one of the most crucial pathways in lung cancer metastasis. Targeting its pathway is decisive in lung cancer research. Thus, this study demonstrated for the first time a significant and selective anti-metastatic effects of lupeol against lung cancer A549 cells via perturbations in the ERK signaling pathway. Materials and Methods: Human protein targets of lupeol were predicted in silico. Migration and cytotoxicity assays were carried out in vitro. Expression levels of proteins Erk1/2 and pErk1/2 were ensured using Enzyme-Linked Immunosorbent Assay (ELISA). Semi-quantitative RT-PCR technique was used to estimate changes in crucial mesenchymal marker geneexpression levels of Ncadherin and vimentin. Results: Lupeol was found to target ERK and MEK proteins effectively. Despite having no cytotoxic effects, lupeol also significantly inhibited cell migration in A549 cells with decreased expression of the pErk1/2 protein along with N-cadherin and vimentin genes. Conclusion: Lupeol inhibits cell migration, showed no cytotoxic effects on A549 cells, decreased pErk1/2 and EMT gene expression. Thus, it can serve as a potential ERK pathway inhibitor in lung cancer therapeutics.

In vitro and in vivo studies of a novel potential anticancer agent of isochaihulactone on human lung cancer A549 cells

2006 ◽  
Vol 72 (3) ◽  
pp. 308-319 ◽  
Author(s):  
Yi-Lin Chen ◽  
Shinn-Zong Lin ◽  
Jang-Yang Chang ◽  
Yeung-Leung Cheng ◽  
Nu-Man Tsai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Anticancer Agent ◽  
Human Lung ◽  
A549 Cells ◽  
In Vivo Studies ◽  
Human Lung Cancer

scholarly journals DT-13 attenuates human lung cancer metastasis via regulating NMIIA activity under hypoxia condition

2016 ◽  
Vol 36 (2) ◽  
pp. 991-999 ◽  
Author(s):  
Xiao-Hui Wei ◽  
Sen-Sen Lin ◽  
Yang Liu ◽  
Ren-Ping Zhao ◽  
Ghulam Jilany Khan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Metastasis ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Lung Cancer Metastasis

scholarly journals Loss of Smad4 promotes aggressive lung cancer metastasis by de-repression of PAK3 via miRNA regulation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiaohong Tan ◽  
Lu Tong ◽  
Lin Li ◽  
Jinjin Xu ◽  
Shaofang Xie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Metastasis ◽  
Human Lung ◽  
Inverse Correlation ◽  
Underlying Mechanism ◽  
Human Lung Cancer ◽  
Mirna Regulation ◽  
Loss Of Function ◽  
Lung Cancer Metastasis ◽  
Metastatic Lung

AbstractSMAD4 is mutated in human lung cancer, but the underlying mechanism by which Smad4 loss-of-function (LOF) accelerates lung cancer metastasis is yet to be elucidated. Here, we generate a highly aggressive lung cancer mouse model bearing conditional KrasG12D, p53fl/fl LOF and Smad4fl/fl LOF mutations (SPK), showing a much higher incidence of tumor metastases than the KrasG12D, p53fl/fl (PK) mice. Molecularly, PAK3 is identified as a downstream effector of Smad4, mediating metastatic signal transduction via the PAK3-JNK-Jun pathway. Upregulation of PAK3 by Smad4 LOF in SPK mice is achieved by attenuating Smad4-dependent transcription of miR-495 and miR-543. These microRNAs (miRNAs) directly bind to the PAK3 3′UTR for blockade of PAK3 production, ultimately regulating lung cancer metastasis. An inverse correlation between Smad4 and PAK3 pathway components is observed in human lung cancer. Our study highlights the Smad4-PAK3 regulation as a point of potential therapy in metastatic lung cancer.

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