ABSTRACT
The elaboration of the mechanism and pharmacodynamic substance are the main obstacles to the modernization of Chinese medicine.The rich ingredient of Chinese medicine is almost attention,with a research strategy of forward pharmacology.This strategy often neglects the study of trace components of Chinese medicine.Synthetic lethality,a extremely complex gene interactions,is to magnify the effects of the co-regulation of biological effects (＞ 1 000 times).The theory of synthetic lethality has achieved good results in the development of anti-tumor drugs,including the discovery of PARP inhibitors,the clinical use of chemotherapy drug addition and attenuation combination.In view of this,this research model may be used to elucidate trace effective substance.Based on the reverse thinking of "targetcomponent-effect"and clear synergistic targets,the mechanism of traces and weak-potency substance of traditional Chinese medicine was studied,and the synergistic combination of potential was found.
ABSTRACT
Tumor metastasis is one of the most important biologi-cal characteristics of malignant tumor, and it is also the main factors that cause treatment failure and poor prognosis. Clinical studies have shown that the number of platelets in patients with malignant tumor increased more significantly than that in benign tumor patients and healthy people, which indicate that platelet might be involved in the development process of tumor. Further study found that in the process of cancer spreading to blood, platelet could interact with tumor cells to form tumor emboli, helped tumor cells escape from immune surveillance, thus pro-moted the tumor metastasis. In recent years, related mechanisms on platelets in promoting tumor metastasis were revealed gradual-ly, and several targeted therapies based on platelets were also carried out. This paper reviews the role of platelet in mediating tumor metastasis by hematogenous spread and its mechanisms and discusses the therapy strategies that target platelet, which may provide references for follow-up research and clinical treat-ment.
ABSTRACT
Aim To screen the potential inhibitors of post-transcriptional activity of pro-inflammatory media-tor TNF-α from the lipophilic constituents in Chinese Medicine Salvia miltiorrhiza Bunge ( Danshen) , we es-tablished dual luciferase reporter gene system pGL3-TNF-α3′UTR ( 3′untranslated region ) co-transfected with Renilla control gene. Methods Complementary DNA ( cDNA) template was obtained from human um-bilical vein endothelial cells ( HUVECs ) . The full length DNA of TNF-α 3′-UTR was amplified through PCR, and then connected the luciferase reporter vector pGL3-control after enzyme digestion. pGL3-TNF-α 3′UTR constructs were co-transfected with pSVRenilla into the mononuclear macrophages RAW264. 7 cells. The relative activity of reporter genes was measured by dual luciferase reporter ( DLR ) assay system after the stimulus of lipopolysaccharide ( LPS ) in presence or absence of tanshinones compounds. Results The pGL3-TNF-α3′UTR luciferase reporter gene was suc-cessfully constructed. The cloning DNA fragment and sequence were both consistent with the GENBANK da-tabase. LPS significantly induced the relative reporter activityof RAW264 . 7 cells transfected with pGL3-TNF-α 3′UTR. Among four tanshinones compounds, we found only cryptotanshinone could significantly de-crease LPS-induced relative reporter activity. Conclu-sion The pGL3-TNF-α 3′UTR construct combined with DLR assay system was successfully established, which can be used to discover the agents such as cryp-totanshinone that regulate the post-transcription of TNF-α in treatment of inflammatory and malignant dis-eases.
ABSTRACT
As the major member of serine/threonine protein ki-nases family, glycogen synthase kinase 3β ( GSK-3β) has well characterized roles in the development of a variety of diseases. However, it is noticed that modulation of GSK-3β in tumor pro-gress is two-faced. Once the activity of GSK-3βas a“pro-onco-genic factor” is inhibited, opposing role as a“tumor suppressor”can also be disrupted, which will trigger the consequent side effect on activation of Wnt/β-catenin signaling pathway. The is-sue has placed a major obstacle to anti-GSK-3β in cancer treat-ment. In fact, functional compartmentalization of a large number of intracellular signaling events cross-talked with GSK-3β can prevent their mutual interference and determine the cell fate. Therefore, understanding the specific mechanisms of GSK-3β in regulation of diverse signaling systems or refinement of a sub-strate competitive inhibitor may have great significance to exploit approaches selectively target GSK-3β in tumor treatment.