scholarly journals Spatial control of oxygen delivery to three‐dimensional cultures alters cancer cell growth and gene expression

2019 ◽  
Vol 234 (11) ◽  
pp. 20608-20622 ◽  
Author(s):  
William J. Wulftange ◽  
Michelle A. Rose ◽  
Marcial Garmendia‐Cedillos ◽  
Davi da Silva ◽  
Joanna E. Poprawski ◽  
...  
2019 ◽  
Author(s):  
William J. Wulftange ◽  
Michelle A. Rose ◽  
Marcial Garmendia-Cedillos ◽  
Davi da Silva ◽  
Joanna E. Poprawski ◽  
...  

ABSTRACTCommonly used monolayer cancer cell cultures fail to provide a physiologically relevant environment in terms of oxygen delivery. Here, we describe a three-dimensional bioreactor system where cancer cells are grown in Matrigel in modified 6-well plates. Oxygen is delivered to the cultures through a polydimethylsiloxane (PDMS) membrane at the bottom of the wells, with microfabricated PDMS pillars to control oxygen delivery. The plates receive 3% oxygen from below and 0% oxygen at the top surface of the media, providing a gradient of 3% to 0% oxygen. We compared growth and transcriptional profiles for cancer cells grown in Matrigel in the bioreactor, 3D cultures grown in 21% oxygen, and cells grown in a standard hypoxia chamber at 3% oxygen. Additionally, we compared gene expression of conventional 2D monolayer culture and 3D Matrigel culture in 21% oxygen. We conclude that controlled oxygen delivery may provide a more physiologically relevant 3D system.


2011 ◽  
Vol 9 (5) ◽  
pp. 660-670 ◽  
Author(s):  
Chen-Yin Ou ◽  
Melissa J. LaBonte ◽  
Philipp C. Manegold ◽  
Alex Yick-Lun So ◽  
Irina Ianculescu ◽  
...  

2014 ◽  
Vol 46 (5) ◽  
pp. 409-414 ◽  
Author(s):  
A. Huang ◽  
B. Bao ◽  
H. R. Gaskins ◽  
H. Liu ◽  
X. Zhang ◽  
...  

2007 ◽  
Vol 27 (13) ◽  
pp. 4968-4979 ◽  
Author(s):  
Dmitri Wiederschain ◽  
Lin Chen ◽  
Brett Johnson ◽  
Kimberly Bettano ◽  
Dowdy Jackson ◽  
...  

ABSTRACT Bmi-1 and Mel-18 are structural homologues that belong to the Polycomb group of transcriptional regulators and are believed to stably maintain repression of gene expression by altering the state of chromatin at specific promoters. While a number of clinical and experimental observations have implicated Bmi-1 in human tumorigenesis, the role of Mel-18 in cancer cell growth has not been investigated. We report here that short hairpin RNA-mediated knockdown of either Bmi-1 or Mel-18 in human medulloblastoma DAOY cells results in the inhibition of proliferation, loss of clonogenic survival, anchorage-independent growth, and suppression of tumor formation in nude mice. Furthermore, overexpression of both Bmi-1 and Mel-18 significantly increases the clonogenic survival of Rat1 fibroblasts. In contrast, stable downregulation of Bmi-1 or Mel-18 alone does not affect the growth of normal human WI38 fibroblasts. Proteomics-based characterization of Bmi-1 and Mel-18 protein complexes isolated from cancer cells revealed substantial similarities in their respective compositions. Finally, gene expression analysis identified a number of cancer-relevant pathways that may be controlled by Bmi-1 and Mel-18 and also showed that these Polycomb proteins regulate a set of common gene targets. Taken together, these results suggest that Bmi-1 and Mel-18 may have overlapping functions in cancer cell growth.


2011 ◽  
Vol 40 (4) ◽  
pp. 935-941 ◽  
Author(s):  
CARMINE SPAMPANATO ◽  
SALVATORE DE MARIA ◽  
MADDALENA SARNATARO ◽  
ELISABETTA GIORDANO ◽  
MARIO ZANFARDINO ◽  
...  

2021 ◽  
Vol 15 (1) ◽  
pp. 19
Author(s):  
Irmanida Batubara ◽  
Arif Rakhman Hakim ◽  
Silmi Mariya ◽  
Suminar Setiati Achmadi ◽  
Valentina Sokoastri Valentina Sokoastri ◽  
...  

Background: 9,10-Anthraquinone (9,10-AQ) is a contaminant on some agricultural products and considered as carcinogenic based on EU Regulation No. 1146/2014. Except for little evidence on experimental rats, there is no strong proof regarding the carcinogenicity in humans. Therefore, it is essential to find a safe dose of this compound since the difference in 9,10-AQ levels will affect cancer cell growth. This research aims to find the 9,10-AQ concentration that does not proliferate the human cancer cells under in vitro study.Methods: In determining the 9,10-AQ concentration that does not proliferate the cancer cells growth, 0.01 to 500 mg/L 9,10-AQ was directly tested on four human cancer cells (colorectal carcinoma HCT 116, colon adenocarcinoma WiDr, breast cancer MCF-7, and cervical cancer HeLa), and the viability of the cells was counted via (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. In the gene expression level, the effects on a selected cancer cell line were determined by qRT-PCR against BAX, BCL-2, PCNA, and P53.Results: The result indicates that 9,10-AQ up to 500 mg/L concentration does not proliferate the cell’s growth but instead inhibits those four cancer cells’ growths. The concentration of 9,10-AQ that inhibits 50% the cancer cells growth (IC50) value was 321.8 mg/L (1.55 mM) against HCT 116 and above 500 mg/L (above 2.40 mM) against WiDr, MCF-7, and HeLa. The 9,10-AQ at 500 mg/L (or 2.40 mM) increases BAX expression and acts as an apoptotic agent on HeLa cells.Conclusions: The investigation has shown that 9,10-AQ up to 500 mg/L concentration does not proliferate the cancer cell growth; instead, it inhibits the HCT 116 and HeLa cells growth. We have preliminary evidence regarding the apoptotic mechanism of 9,10-AQ by increasing BAX gene expression on HeLa cells.


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