1、硒和抗癌医学宣教硒和抗癌医学宣教background Selenium(Se),an essential trace dietary nutrient with anticarcinogenic（抑癌）potential 氧族元素，原子序数34，相对分子量78.96 In foods and dietary supplements:SeMet and SeCys,smaller amounts of methylated selenides are dominant forms of Se2硒和抗癌医学宣教Fig.14硒和抗癌医学宣教main points of the Selenium me
2、tabolism absorb and retain Se better from SeMet and Se yeast than from the inorganic Se salts Selenide has a central role in Se metabolism,being the branch point of two metabolic pathways:selenoprotein production and selenoprotein excretion(排泄)CH3SeH and CH32SeH：excreted across the lungs（肺）CH33Se+an
3、d CH3Se-GalN,excreted across the kidney（肾）5硒和抗癌医学宣教main points of the Selenium metabolism SAM是生物体内广泛存在的重要中间代谢物质，参与体内众多重要生化反应。作为生物体代谢的主要甲基供体-lyase是一种裂合酶6硒和抗癌医学宣教the discovery of selenium functionsSchwarz发现某些天然物质能够防止大鼠食饵性坏死Schwarz和 Foltz均证明，硒是防止食饵性肝坏死的一种保护因子Roctrack和 Hoekstra证明，硒是谷胱甘肽过氧化物酶的活性成分20世70年代
4、初，中国克山病研究工作者发现克山病与处于贫硒状态有关，采用硒盐之后，对克山病有预防作用世界卫生组织（WHO）1973年确认硒是人类生命必须 14种微量元素的第一种微量元素，缺硒会严重影响人的身体健康7硒和抗癌医学宣教 the discovery of selenium functions It was first suggested in the late 1960s that Se might also be anticarcinogenic,based on an inverse relationship of Se status and risks of some kinds of ca
5、ncer Interest in this area was stimulated by the landmark finding that supplementation of free-living people with Se-enriched brewers yeast（啤酒发酵液）with predominantly selenomethionine(SeMet)decreased the overall cancer morbidity by nearly 50%8硒和抗癌医学宣教 the discovery of selenium functions That finding c
6、ame from the Nutritional Prevention of Cancer(NPC)trial,a prospective(有预计的),double-blinded（双盲的）,randomized（随机的）,placebo-controlled(有安慰剂对照的)trial involving 1312 patients recruited because of histories of nonmelanoma skin cancers（非黑色素瘤性皮肤癌）To follow-up on that finding,the Se and Vitamin E Chemoprevent
7、ion Trial(SELECT)was launched in the fall of 2001.This is a randomized,double-blind,designed to determine whether Se(as SeMet)and vitamin E,alone or in combination,can reduce the risk of prostate cancer among 32,400 healthy men9硒和抗癌医学宣教summary：selenium functions antioxidant protection(via selenoprot
8、eins),altered carcinogen metabolism,enhanced immune surveillance,regulation of cell proliferation and tumor cell invasion and inhibition of neoangiogenesis(血管异生)In addition,Se has been shown to mediate a number of insulinlike（类似胰岛素）actions including the stimulation of glucose uptake and regulation o
9、f glycolysis(糖酵解),gluconeogenesis（糖异生）,fatty acid synthesis and the pentose phosphate pathway（磷酸戊糖途径）10硒和抗癌医学宣教Different dose,different functionAny of these forms can support the nutritional requirements for the element;however,their bioefficacy depends on both dose and chemical form，specially the C
10、H3SeH 0.10.2 ppm as an essential micronutrient 5 ppm becomes toxic 55 ug/day daily allowance 100200 ug/day inhibit genetic damage and cancer development in human subjects 400 ug/day upper safe limit11硒和抗癌医学宣教Different dose,different function At low doses,Se function is an essential component of SeCy
11、s in several specific selenoproteins and promote cell proliferation,a fact of particular importance to the immune response.At higher doses,but still nontoxic,Se can reduce cancer risk.This effect involves the stimulation of tumor cell cycle arrest and apoptosis and the inhibition of tumor cell migra
12、tion and invasion12硒和抗癌医学宣教Fig.213硒和抗癌医学宣教low doses：cell proliferation When HL-60 cells were optimized in serum-free culture conditions to maximize the effects of Se on cell growth,low levels of Se(nmol/L)enhanced cell proliferation and up-regulated the expression of numerous cell cycle-related gene
13、s,including as c-Myc,cyclin C,proliferating cell nuclear antigen,cyclin-dependent kinase(CDK)1,CDK2,CDK4,cyclin B and cyclin D2 mRNA and total cellular phosphorylated proteins14硒和抗癌医学宣教 Furthermore,when Jurkat cells were cultured in a serum-free(Sedeficient)medium,selenoenzyme activities such as GPx
14、 and TrxR decreased significantly within cells and subsequently induced cell death.Interestingly,a lipid soluble radical-scavenging antioxidant(vitamin E)but not the water-soluble antioxidants(ascorbic acid,N-acetyl cysteine and glutathione),completely blocked Se deficiency-induced cell death,althou
15、gh vitamin E could no restore Sedependentenzyme activity15硒和抗癌医学宣教 The insulinlike actions of Se include increasing glucose uptake and adenosine triphosphate generation through the activation of glycolysis,up-regulation of antiapoptotic protein Bcl-2,maintenance of mitochondrial membrane potential,s
16、timulation of fatty acid synthesis and pentose phosphate pathway activity16硒和抗癌医学宣教Special about the CH3SeH 人体的正常血管是直线型，而肿瘤血管是螺旋形，血管内的血液流量变多，血液的压力变大，血液流速快，肿瘤吸收营养的速度自然也就加快，瘤体因此迅速疯长。人体的正常血管生长周期是一年，而肿瘤血管的生长周期只有4天，也就是说，只需要4天的时间，肿瘤血管就能生长出来，破坏人体的正常组织，直接造成病人病灶部位的疼痛。癌细胞的转移，有两个渠道，一个是淋巴道转移，只能转移到附近组织，所以危害相对较小；
17、另外一个，危害巨大，那就是血管转移，事实上，90%的癌症患者，都是死于血道转移，这也是肿瘤血管造成的最大危害。肿瘤血管，是癌细胞的营养通道和转移途径17硒和抗癌医学宣教Special about the CH3SeH Methylselenol precursors exert rapid,inhibitory effects on the expression of key molecules involved in angiogenesis regulation.For example,it was demonstrated that subapoptotic doses of MSeA inhibited the expression and secretion of vascular endothelial growth factor(VEGF,an angiogenic factor),in several cancer cell lines and inhibited MMP-2 and VEGF expression in vascular endothelial cells18硒和抗癌医学宣教
