Consequently, this pathway is commonly deregulated in cancer. In particular, mutations in the gene PIK3CA that encodes the p110α catalytic subunit of the PI3K enzymes result in cell proliferation and resistance to apoptosis in vitro and induce breast

tumors in transgenic mice. These data underscore the 点击此处 role of this pathway during oncogenesis. Thus, an ongoing, large-scale effort is underway to develop clinically active drugs that target elements of the PI3K pathway. However, conflicting data suggest that gain-of-function PIK3CA mutations may be associated with either a favorable or a poor clinical outcome, compared with the wild-type PIK3CA gene. In the current study, we performed a systematic review of breast cancer clinical studies. Upon evaluation of 2587 breast cancer cases from 12 independent studies, we showed that patients with tumors harboring a PIK3CA mutation have a better clinical outcome than

或者 those with a wild-type PIK3CA gene. Importantly, this improved prognosis may pertain only to patients with mutations in the kinase domain of p110α and to postmenopausal women with estrogen receptor-positive breast cancer. We propose three potential explanations for this paradoxical observation. First, PIK3CA mutations may interfere with the metastasis process or may induce senescence, which results in a better outcome for patients with mutated tumors. Secondly, we speculate

that PIK3CA mutations may increase early tumor diagnosis by modification of the actin cytoskeleton in tumor cells. Lastly, we propose that PIK3CA mutations may be a favorable predictive factor for response to hormonal therapy, giving a therapeutic advantage to these patients. Ultimately, an improved understanding of the clinical impact of PIK3CA mutations is critical for the development of optimally personalized therapeutics against breast cancer and other solid tumors. This 或者 effort will be important to prevent or explain therapeutic failures and select patients who are most likely to respond to new therapies that inhibit the PI3K pathway.
目的研究吲哚-3-甲醇(I3C)的重要衍生物3,3’-二吲哚甲烷(DIM)对宫颈癌SiHa细胞增殖和凋亡的影响。方法采用CCK-8法检测不同浓度DIM对SiHa细胞体外生长的抑制作用,流式细胞术检测DIM对SiHa细胞凋亡的影响,荧光显微镜观察细胞形态的变化;Western blotting检测不同浓度DIM对SiHa细胞凋亡相关蛋白表达的影响。结果 DIM对SiHa细胞的抑制作用呈时间-剂量依赖性,DIM对SiHa细胞干预48h的半数抑制浓度(IC50)为44.44μmol/L。分别以25、50、100μmol/L的DIM处理48h后,SiHa细胞的凋亡率分别为(10.09±1.32)%、(21.11±3.36)%和(55.46±6.33)%,阴性对照组为(4.56±0.