Nsitizer. Further work is needed to determine the molecular properties of the radiation DNA-PK cancer reaction verst with AZD6244 predict RKT. Because AZD6244 treatment with Ver Changes in cell cycle-associated modifiers was, we investigated whether the effects of the cell cycle, the observed increase in the radiation sensitivity of the presence of AZD6244 may be explained Ren. Pretreatment of cells not with AZD6244 as in clonogenic assays of cells redistribute radiosensitive G2 and M phase of cell cycle, suggesting that reassortment was not in a sensitive phase of the cell cycle of the mechanism for responding to increased Hte radiation. In contrast, after irradiation of the cell cycle analysis showed that treatment of the cells entered with AZD6244 Born by a increased Hte mitotic index as compared to vehicle-treated cells, suggesting that AZD6244-treated cells had a reduction in the activation of the control point the G2 / M after irradiation.
The activation of the G2 arrest is considered to induce protection against cell death by radiation. on the observation that the activation AZD6244 treatment G2 checkpoint support after the irradiation, inhibits ERK1 / 2 activation is necessary to arrest for carcinoma cells in the G2 checkpoint via Chk1 path. We found that AZD6244 treatment led to a reduction in pre-irradiation of Chk1, phosphorylated probably a factor in the G2 checkpoint repealed. Mitogen-activated protein kinase is one of the critical molecules of the Ras / Raf / MEK / ERK cascade, signal transduction mediated by Ras / Raf to extracellular Signal regulated kinases by re phosphorylation of tyrosine residues and two threonine protein kinase ERK.
Humans and other S uger Two proteins MEK, MEK1 and MEK2, which are encoded by the corresponding genes, expressed and ubiquitously.6 The constitutively active form of MEK is sufficient for the cellular Re transformation, such as by a number of highly tumorigenic cells detected lines.7, 8 Furthermore, activation of the MEK / ERK has to develop a variety of human tumors, including normal lung cancers.9, put 10 in conjunction erh hte activation of MEK / ERK in 30 identified, 60% of prim Ren lung cancer, 9.11 14 is provided with a hyperactivation satisfied t, that the overexpression is associated with ERK, and is associated with poor survival.
12 the R is important for the Ras / Raf / MEK / ERK in tumor development, to clinical trials of MEK inhibitors for the treatment of various solid tumors, including normal lung led cancers.15, resulted in 16 Health Centres Umen disease stabilization in a small subgroup of patients with lung cancer, melanoma, pancreatic cancer or c . lon Clinical studies have shown, however, is that the inhibition of ERK in the tumor tissue of the patient, the MEK inhibitor, phosphorylation does not correlate with clinical benefit, 17 indicating that both the presence of activated ERK before the treatment and suppression of ERK activation after the treatment is not sufficient to lead to selection of patients and predict response to treatment with the MEK inhibitors. Therefore, molecular biomarkers that predict the response to MEK inhibitors L Sst needed to improve the design of future clinical trials of these agents and evaluation of results, and optimize the results of the targeted lung cancer treatment with MEK inhibitors. The identification of molecules,