Although surgical resection combined with adjuvant therapy is effective at the early stages of the disease,resistance

to conventional therapies is frequently observed in advanced stages,where treatments become ineffective.Resistance to cisplatin,irinotecan and 5-fluorouracil chemotherapy has been shown to involve mitogen-activated protein Protein Tyrosine激酶抑制剂 kinase(MAPK)signaling and recent studies identified p38αMAPK as a mediator of resistance to various agents in CRC patients.Studies published in the last decade showed a dual role for the p38αpathway in mammals.Its role as a negative regulator of proliferation has 此网站 been reported in both normal(including cardiomyocytes,hepatocytes,fibroblasts,hematopoietic

and lung cells)and cancer cells(colon,prostate,breast,lung tumor cells).This function is mediated by the negative regulation of cell cycle progression and the transduction of some apoptotic stimuli.However,despite its anti-proliferative and tumor suppressor activity in some tissues,the p38αpathway may also acquire an oncogenic role involving cancer related-processes such as cell metabolism,invasion,inflammation and angiogenesis.In this review,we summarize current knowledge about the predominant role of the p38αMAPK pathway in CRC development and chemoresistance.In our view,this might help establish the therapeutic potential of the targeted manipulation of this pathway in clinical settings.
随着当今社会的发展,心血管疾病已成为影响人类生命的首位重大疾病。尽管最近内外科治疗有较大的进展,但因心血管病而住院的患者人数却逐年增加[1]。针对基因和蛋白的探索,为防治心血管疾病,提供新的治疗思路和潜在的药物靶点。1 14-3-3蛋白简介14-3-3蛋白家族,是一类高度保守的酸性蛋白,最早由Moore等于1967年为寻找在大脑组织中特异表达的蛋白而发现,并根据DEAE-cellulose chromatography和电泳分离
目的探讨p38丝裂原活化蛋白激酶(p38MAPK)通路与细胞空泡形成的关系。方法应用茴香霉素、放线菌酮、p38MAPK抑制剂SB203580、JNK抑制剂SP600125处理HepG2、LM3、QBC939、Hela和A549细胞,光学显微镜和激光共聚焦显微镜观察细胞空泡化情况;Western

blot法检测p38MAPK等通路相关分子的表达水平;内质网红色荧光探针标记内质网,激光共聚焦显微镜观察内质网结构变化;溶酶体红色荧光探针标记溶酶体,激光共聚焦显微镜观察溶酶体荧光染色情况。结果 (1)茴香霉素对HepG2细胞空泡有消除作用。(2)茴香霉素通过活化p38MAPK消除细胞空泡。(3)阻断p38MAPK诱导多种肿瘤细胞空泡形成。(4)阻断p38MAPK介导的空泡形成破坏内质网结构的整体性。(5)阻断p38MAPK介导的空泡形成具有可逆性。结论 NVP-BEZ235 p38MAPK通路在调节细胞空泡形成中发挥了重要作用。
Objective To investigate the role of IQ domain GT Pase-activating protein 1(IQGAP1)in angiotensinⅡ(AngⅡ)-induced podocyte apoptosis and the underlying mechanism.Methods Differentiated mouse podocytes were exposed to AngⅡat different concentrations for 6 h or at 10-8mol/L for variable incubation time.Podocyte apoptosis was assessed by flow cytometry.