Resistance to chemotherapy remains a big challenge in e treatment of metastatic UC. Identify the mechanisms of resistance, and the development of novel therapeutic agents are important in the treatment of colitis, ulcerative colitis. Tats In this study, exposure of human cells to celecoxib-induced UC Chlich UPR activation. Celecoxib induced UPR in cells of human UC connected to the regulation of GRP78. GRP78 removable by siRNA or chemical inhibition can potentiate the cytotoxic effect of Alvocidib Flavopiridol celecoxib and apoptotic cells in UC. Moreover LM1685 not regulate GRP78 as celecoxib, no more than it has cytotoxicity t Unified Communications in human cells to induce. However, GRP78 has indeed increased knockdown Hen the cytotoxicity t of celecoxib and reverse resistance LM1685. Our results show that r Essential role in the protection of GRP78 in cancer cell apoptosis inhibitorinduced COX second Downregulation of GRP78 can k Significantly improve the sensitivity of t to the inhibitor of COX-2 in the cells of Unified Communications. The ubiquitin-proteasome pathway other intracellular Other proteins cellular Re Hom Homeostasis w During the stress experience UPR hold. A previous study showed that the combination of a proteasome inhibitor MG132 celecoxib and synergistic anti-proliferative effect in human tumor cells of the liver erm Glicht. In the present study, we found that the combined treatment with MG132 k in human cells UC Nnte The cytotoxicity t of celecoxib potentiate with simultaneous induced down-regulation of GRP78.
Celecoxib is usually t orally at a dose of 200 mg twice Administered resembled that caused it to mean serum 1 2 mM. Side effects of celecoxib at therapeutic doses include kardiovaskul Ttchenaggregation re thrombosis, congestive heart failure, gastrointestinal ulceration, renal or hepatic injury and Pl. Some reports on the side effects of celecoxib in supratherapeutic clinical study showed that there were no significant side effects supratherapeutic doses. In our study, using in vitro methods, we chose 100 mM concentrations of celecoxib as a working language, a concentration much h Ago as the concentration corresponding to the maximum recommended dose FDA. This is consistent with a variety enzalutamide of studies on antitumor activity of celecoxib in vitro show that celecoxib concentration required to inhibit the growth of cancer cells in vitro is much hour ago Than ben in vivo bubble CONFIRMS and other cancers. This difference means that the growth of tumors in vivo, by intrinsic interaction between factors on tumor cells and extrinsic factors such as extracellular Ren matrix, stromal cells and is determined by other factors, h Yourself. This U Eren factors are typically missing in vitro conditions. Cell culture models are often used to evaluate the therapeutic potential of COX-2 for cancer, but it should be noted that to be used in vitro results, particularly with respect to the relative dose of the composition, k Can not be extrapolated directly to the entire organism . In summary, this study showed that celecoxib can significantly inhibit cell proliferation of unified communications people. Stress exacerbates the unfolded protein by downregulation of GRP78 or proteasome inhibitor further improve apoptosis induced by celecoxib caused CPU. These results are promising