动物实验,癌细胞衰老 z-bo 2020-08-31 465

　　The human adaptive immune system plays an important role in the control of cancer and has been widely recognized. People have been working on developing effective targeted cancer immunotherapy. Many of these treatment methods do not eliminate cancer cells through cytotoxicity, but instead inhibit the growth of cancer cells.

　　Martin from the University of Tubingen, Germany? Under the leadership of a research team, Cken discovered a new type of TH1 cell in a new study that can prevent the growth of cancer cells and clarified the molecular mechanism of these cells.

　　cken et al. conducted an experimental study using a transgenic mouse model. The mouse model tumor antigen Tag is expressed under the control of the rat insulin promoter and can cause aggressive β-cell carcinoma by partially or completely silencing the tumor suppressor p53 and Rb. The researchers found that only CD4 + TH1 cells that secrete TNF and IFN-g can inhibit the growth of these tumors. This will double the life of the mouse. The researchers found that mouse tumor cells treated with sham surgery can continue to grow, while mouse tumor cells treated with TH1 cells cannot grow in vitro. Next, the researchers co-cultured β cancer cells from sham-treated mice with TNF and IFN-g or a control medium. Three days later, the cytokine-treated cells stagnated in the G1/G0 phase of the cell cycle. I found. In contrast, more than 25% of cells that have not been treated with these cytokines enter the S phase, indicating that they are proliferating at a high rate. As we all know, G1/G0 tumor cell arrest is a sign of cell senescence. Therefore, the researchers further investigated whether the cytokines IFN-g and TNF can cause long-term tumor senescence and growth arrest. They washed the cells treated with cytokines for 5 days and then cultured them for another 2 weeks. The researchers found that these cells can age completely for two weeks, and during this period, cells that have not been treated with cytokines grow rapidly. In these cytokine-treated cells, the researchers also observed changes in gene expression patterns and epigenetic changes related to cell aging. The researchers observed the expression of early senescence marker genes such as pHP1c after 3 days of IFN-g and TNF treatment. After 4 days of cytokine incubation, the expression of senescence-related b-galactosidase (SA-b-gal) and other late senescence genes and stable growth arrest were observed. Treatment with IFN-g or TNF alone may cause some related changes in gene expression, but it is not enough to cause long-term growth arrest. In addition, the researchers found that the transcription factor STAT1 and TNF receptor TNFR1 (also known as CD120) activate the p16INK4a target protein downstream of JUNB. This signal transduction is a necessary condition for cytokines that induce senescence. In addition, the researchers found that IFN-g and TNF induce the expression of p16INK4a and promote the phosphorylation of the tumor suppressor protein RbSer795. This series of changes induced the senescence of β cancer cells by stabilizing the p16INK4a–Rb signal. Researchers have confirmed that beta cancer cells lacking STAT1 or TNFR1 will not enter a state of senescence after being given IFN-g and TNF. Researchers have also observed several other mouse and human cell lines, as well as naturally regressing human melanoma cells, and this cytokine-induced senescence plays a role in tumor immunology. The meaning is wide and it has the potential to be realized. For testing

　　Can TH1 cytokines induce tumor senescence in vivo, R? Ken et al transplanted different β cancer cell lines into immunodeficient mice. In mice treated with Tag-TH1 cells, β cancer cells failed to grow after transplantation, and similar cells that did not express TNFR1 were found to grow actively in the mice. These results indicate that IFN-g and TNF secreted by TH1 cells drive the senescence mechanism of tumor cells through the p16INK4a-Rb signaling pathway, which is specific in certain types of tumors. Therapies that stimulate TH1 immunity are responsible for its clinical effects.