Dipeptidyl peptidase-4 apoptotic cells increased to 29% in transfected cells

M. also reduced by transfection dnAKT IC50 value of 169.3 m to 1.8 m in H522 cells. Cell cycle analysis of these cells showed that transfection with dnAKT led to a dramatic increase in apoptosis induction by AZD6244. In both HCC2450 and H522 cells, treatment with 10 Dipeptidyl peptidase-4 M of AZD6244 was effective for 3 days Born to background levels of apoptotic cells in parental and vector-transfected cells. In contrast, apoptotic cells increased to 22% 29% in transfected cells, dnAKT Similar as observed in sensitive cells. This result shows that produce the inhibition of AKT k Can sensitivity to AZD6244 in resistant cells again. Discussion AZD6244 is a small synthetic inhibitor tyrosine kinases which is selective for MEK1 / 2. It has been studied in clinical trials for the treatment of melanoma, colon cancer or advanced NSCLC.
Although the cytotoxicity t has been observed in cancer cells, AZD6244, 18 20 occurs and the intrinsic resistance to this compound, and molecular biomarkers that predict response to this agent may be useful can k Clinically. It was previously suggested that mutations in the BRAF, BRAF mutation, especially in relation to sensibility T for different MEK inhibitors in cancer cells.21 Raf mutations activating proteins, direct upstream activators of MEK expected to result in reported Erh relationships of the MEK / ERK activity t. It is therefore conceivable that the suppression of inhibiting the MEK per survival function of the activation of Raf protein. Clinical studies have shown that both the presence of activated ERK and suppression of ERK activation after the treatment is not sufficient to predict the benefit of treatment with MEK inhibitors.
17 We found that ERK phosphorylation was AZD6244 were the cells of both in anf lligen resistant and removed, suggesting that resistance to the MEK inhibitors caused not by MEK / ERK activity th itself. Indeed, Solit et al. observed a hnlichen degree of ERK p deletion in sensitive and resistant cells with both MEK inhibitor CI 1040 treated, although cyclin D1 downstream rtigen molecule was removed from the sensitive cells but not in resistant cells.21 In this study, we knew not observe a correlation between BRAF mutations and AZD6244 sensitivity, all the cell lines analyzed here BRAF wild-type. Recent studies have shown that inhibition of ERK activated feedback between defect and Raf, which can not MEK upregulates caused in BRAF mutant cells resistant AZD6244.
22, 23 Our study found linked to upregulation of p MEK after treatment with AZD6244 was more dramatic in the sensitive cell lines than in resistant cell lines, suggesting that upregulation of MEK comments k can not play an R to AZD6244 in resistance. In this study, we found that resistant cells AZD6244 high p AKT, that of expressing sensitive cells. Both give the Ras / Raf / MEK / ERK pathway and PI3K/Akt signals from different receptors for growth factors. Interestingly, these two pathways regulate several common downstream molecules that are essential for the survival of the cell and the cell cycle is shown. For example, to regulate both pathways regulate the expression of cyclin D1, 24.25, and both phosphorylation and expression of transcription factors fork head 26 28 31 Bad29 caspase 9,32,33 and the game all the r Fundamentals of apoptosis. Do

Leave a Reply

Your email address will not be published. Required fields are marked *


You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <strike> <strong>