RESUMEN
The MYC gene, one of the most common dysregulated driver genes in human cancers, is composed of three paralogous genes C-MYC, N-MYC and L-MYC. It is abnormally activated in more than half of cancer types. Since MYC plays an important role in the formation, maintenance and progression of cancer, targeting MYC is an effective strategy for cancer treatment. As a potential anti-cancer target, MYC is considered "undruggable" because it lacks a suitable pocket for accommodating small molecule inhibitors. Recently, under the guidance of protein structure information and many computational tools, many indirect strategies to inhibit MYC have emerged and shown favorable anti-cancer effects in tumor models. In this paper, the recent small molecules that indirectly target MYC are divided into inhibitors acting on the protein-protein interaction (PPI) among MYC and other proteins, and targeting inhibitors regulating MYC action. Additionally, the introduction and assessment towards compounds with different mechanisms are summarized to provide reference for the further research of MYC inhibitors.
RESUMEN
Objective To observe the expression of Myc associated factor X (MAX) in aortic dissection tissue, and to discuss its biological functions. Methods MAX expression level was evaluated by qRT-PCR and Western blotting analysis in 15 dissected aorta samples. The adenovirus vector was used to transfect human aortic smooth muscle cells (HASMCs) for overexpression of MAX. The effects of MAX overexpression on proliferation and apoptosis of HASMCs were analyzed by Cell Counting Kit-8 and flow cytometry, respectively. Results MAX mRNA and protein expression levels were significantly higher in the aortic dissection tissue compared with that in the healthy controls. Overexpression of MAX significantly inhibited the proliferation of HASMCs and promoted its apoptosis (P<0.05). Conclusion MAX might induce the loss of HASMCs via regulating their proliferation and apoptosis process, thus play an important role in the development and progression of aortic dissection.
RESUMEN
Objective To establish a model of pancreatic cancer induced by 7,12-dimethylbenzathracene (DMBA) in SD rats, and to detect the expression levels of RAD51 and Myc-associated factor X (MAX) and their effect on carcinogenesis of rat pancreas. Methods Ninety SD rats were randomly divided into 3 groups: a model group, an intervention group, and a control group. DMBA was directly implanted into the parenchyma of rat pancreas (the model group and the intervention group). Rats in the intervention group were treated with 1 mL trichostatin A (TSA) saline solution (1 μg/mL) via ip weekly. Rats within 3～5 months in the model group and the intervention group were executed and observed by macrograph and under microscope. Meanwhile, the rats in the control group were executed at 5th month. The EnVision~(TM) immunohistochemistry to assay the expression levels of RAD51 and MAX was used in conventional paraffin-embedded sections from the above pancreatic specimens.Results The incidence of pancreatic cancer in the model group within 3-5 months was 48.7% (18/37), including 17 ductal adenocarcinomas and 1 fibrosarcoma. The incidence of pancreatic cancer in the intervention group within 3-5 months was 33.3%(12/36), including 11 ductal adenocarcinomas and 1 fibrosarcoma. The maximal diameter of mass in the model group was significantly higher than that in the intervention group (P＜0.05). No pathological changes were found in pancreas of the control group and other extra-pancreatic main organs of the model group and the intervention group (such as the liver, biliary tract, gastrointestine tract, kidney, and lung). The positive rate of RAD51 was significantly higher in ductal adenocarcinoma in the model group, the intervention group, and the model group +the intervention group than those in corresponding groups of non-cancerous pancreatic tissues (P＜0.01), but the positive rate of MAX expression was opposite to RAD51 expression(P＜0.01). The positive tissues of RAD51 expression and/or negative tissues of MAX expression in non-cancerous tissues showed atypical-hyperplasia of ductal epitheli. Pacncreas of the control group showed the negative expression of RAD51 and positive expression of MAX. Two cases of fibrosarcoma showed the negative expression of RAD51 and MAX.Conclusion DMBA directly implanted into the parenchyma of pancreas can obtain an ideal pancreatic cancer model with high incidence in a short time. The TSA might have an inhibitive effect on carcinogenesis and growth of rat pancreas. The over-expression of RAD51 and/or lose-expression might have important effect on carcinogenesis induced DMBA in rat pancreas.