scholarly journals Polychlorinated biphenyls induce adhesion of breast cancer cells to human brain endothelium through lipid raft‐dependent upregulation of cell adhesion molecules

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Sung Yong Eum ◽  
Yean Jung Choi ◽  
Masa Radakovic ◽  
Ibolya E Andras ◽  
Bernhard Hennig ◽  
...  
Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 309 ◽  
Author(s):  
Maeirah Afzal Ashaie ◽  
Rowshan Ara Islam ◽  
Nur Izyani Kamaruzman ◽  
Nabilah Ibnat ◽  
Kyi Kyi Tha ◽  
...  

While several treatment strategies are applied to cure breast cancer, it still remains one of the leading causes of female deaths worldwide. Since chemotherapeutic drugs have severe side effects and are responsible for development of drug resistance in cancer cells, gene therapy is now considered as one of the promising options to address the current treatment limitations. Identification of the over-expressed genes accounting for constitutive activation of certain pathways, and their subsequent knockdown with specific small interfering RNAs (siRNAs), could be a powerful tool in inhibiting proliferation and survival of cancer cells. In this study, we delivered siRNAs against mRNA transcripts of over-regulated cell adhesion molecules such as catenin alpha 1 (CTNNA1), catenin beta 1 (CTNNB1), talin-1 (TLN1), vinculin (VCL), paxillin (PXN), and actinin-1 (ACTN1) in human (MCF-7 and MDA-MB-231) and murine (4T1) cell lines as well as in the murine female Balb/c mice model. In order to overcome the barriers of cell permeability and nuclease-mediated degradation, the pH-sensitive carbonate apatite (CA) nanocarrier was used as a delivery vehicle. While targeting CTNNA1, CTNNB1, TLN1, VCL, PXN, and ACTN1 resulted in a reduction of cell viability in MCF-7 and MDA-MB-231 cells, delivery of all these siRNAs via carbonate apatite (CA) nanoparticles successfully reduced the cell viability in 4T1 cells. In 4T1 cells, delivery of CTNNA1, CTNNB1, TLN1, VCL, PXN, and ACTN1 siRNAs with CA caused significant reduction in phosphorylated and total AKT levels. Furthermore, reduced band intensity was observed for phosphorylated and total MAPK upon transfection of 4T1 cells with CTNNA1, CTNNB1, and VCL siRNAs. Intravenous delivery of CTNNA1 siRNA with CA nanoparticles significantly reduced tumor volume in the initial phase of the study, while siRNAs targeting CTNNB1, TLN1, VCL, PXN, and ACTN1 genes significantly decreased the tumor burden at all time points. The tumor weights at the end of the treatments were also notably smaller compared to CA. This successfully demonstrates that targeting these dysregulated genes via RNAi and by using a suitable delivery vehicle such as CA could serve as a promising therapeutic treatment modality for breast cancers.


Nano LIFE ◽  
2012 ◽  
Vol 02 (03) ◽  
pp. 1241009 ◽  
Author(s):  
AMITA DAVEREY ◽  
AUSTIN C. MYTTY ◽  
SRIVATSAN KIDAMBI

This article demonstrates that the surface micro-topography regulates the biology of breast cancer cells, including the expression of HER-2 gene and protein. The breast tumor microenvironment is made up of heterogenous mixture of pores, ridges and collagen fibers with well defined topographical features. Although, significant progress has been achieved towards elucidating the biochemical and molecular mechanisms that underlie breast cancer progression, quantitative characterization of the associated mechanical/topographical properties and their role in breast tumor progression remains largely unexplored. Therefore, the aim of this study is to investigate the effect of topography on the adhesion and biology of breast cancer cells in in vitro cultures. Polydimethylsiloxane (PDMS) surfaces containing different topographies were coated with polyelectrolyte multilayers (PEMs) to improve cell adhesion and maintain cell culture. HER-2 expressing breast cancer cells, BT-474 and SKBr3, were cultured on these PDMS surfaces. We demonstrate that micro-topography affects the cell adhesion and distribution depending on the topography on the PDMS surfaces. We also report for the first time that surface topography down-regulates the HER-2 gene transcription and protein expression in breast cancer cells when cultured on PDMS surfaces with micro-topographies compared to the tissue culture polystyrene surface (TCPS) control. Results from this study indicate that micro-topography modulates morphology of cells, their distribution and expression of HER-2 gene and protein in breast cancer cells. This study provides a novel platform for studying the role of native topography in the progression of breast cancer and has immense potential for understanding the breast cancer biology.


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