Release date: 2016-11-29
During the development and growth of tumors, due to the rapid growth of tumors, the nutrients and oxygen that are transported by blood vessels are insufficient, which promotes the evolution of tumor cells to adapt to the hypoxic environment. In order to survive and grow in a hypoxic environment, tumor cells will synthesize more hypoxia-inducible factor 1 (HIF-1). HIF-1 can promote a series of changes in cell function by sensing the decrease of oxygen level, including changing metabolic patterns and transmitting signals that promote new angiogenesis. Therefore, it is currently believed that tumors in the hypoxic environment mainly rely on the function of HIF-1 to survive and grow. .
Based on this, Professor Ali Tavassoli of the University of Southampton and his colleague Ishna Misry led a new study published in the journal ACS Synthetic Biology. He explained: "To better understand HIF-1 in tumors. To play a role and fully demonstrate the potential of inhibiting this protein in tumor therapy, we genetically engineered a human cell and added a genetic loop that promotes HIF-1 production in a hypoxic environment. Inhibiting molecules."
"We have successfully engineered a genetically engineered cell that produces a HIF-1 inhibitory molecule that inhibits HIF-1 function in cells. As expected, its expression limits the survival of cells in a nutrient-deficient environment. Growing."
"From a larger perspective, we have given these genetically engineered cells a ability to fight back - to inhibit the function of a key protein in tumor cells. This may lead to the generation and use of the 'sentinel circuit', this 'sentinel The loop 'can generate bioactive molecules that can target a range of diseases including tumors based on changes in the environment or cellular state."
This gene loop is chimeric in the chromosome of a human cell line and encodes the RNA required for this cyclic peptide HIF-1 inhibitor, which can be produced by hypoxia stimulation. The team found that even if this factor is produced directly in the cell, it can also inhibit the downstream signal of HIF-1 and inhibit these cells from adapting to the hypoxic environment.
The next step for these researchers is to determine the possibility that this method will produce tumor suppressor and inhibit tumor growth in tumor models.
Professor Tavassoli stressed: "The main application of this work is to avoid our own synthesis and addition of inhibitors, so that biologists can use our method to more easily study the function of HIF-1, and perhaps find HIF-1 in tumors. More features. This also allows us to know if the ability to suppress HIF-1 alone in the relevant tumor model is sufficient to inhibit tumor growth. Another interesting aspect of this work is that it reveals the possibility that we may be in the future. New reaction mechanisms can be added to human cells to allow cells to respond to disease signals and self-synthesize therapeutic drugs for self-treatment."
Source: Translational Medicine Network
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