石 芳,廖 霞,李 瑤,李 謠,肖星凝,吳素蕊,明 建,,3,*
(1.西南大學食品科學學院,重慶 400715;2.中華全國供銷合作總社昆明食用菌研究所,云南 昆明 650223;3.重慶市特色食品工程技術(shù)研究中心,重慶 400715)
植物多酚通過PI3K/Akt信號通路抗腫瘤作用研究進展
石 芳1,廖 霞1,李 瑤1,李 謠1,肖星凝1,吳素蕊2,明 建1,2,3,*
(1.西南大學食品科學學院,重慶 400715;2.中華全國供銷合作總社昆明食用菌研究所,云南 昆明 650223;3.重慶市特色食品工程技術(shù)研究中心,重慶 400715)
磷脂酰肌醇3-激酶/絲氨酸/蘇氨酸激酶B(phosphatidylinositol 3-kinase/serine/threonine kinase B,PI3K/Akt)信號通路是一條經(jīng)典的抑制細胞凋亡、促進細胞增殖的信號轉(zhuǎn)導通路,在腫瘤、心血管疾病、神經(jīng)系統(tǒng)疾病和糖尿病等的防治中發(fā)揮重要作用,特別是腫瘤。PI3K/Akt信號通路的異?;罨c腫瘤的發(fā)生、侵襲和轉(zhuǎn)移等過程密切相關(guān),對該通路的研究已成為當今國內(nèi)外治療腫瘤的焦點。植物多酚因具有抗腫瘤作用而成為預防腫瘤的天然藥物。本文綜述了PI3K/Akt信號通路的結(jié)構(gòu)、活化機制以及與腫瘤的關(guān)系,總結(jié)植物多酚通過該信號通路對腫瘤細胞的作用機制,以期為研發(fā)植物多酚作為預防腫瘤的保健食品或藥品提供一定的科學依據(jù)。
磷脂酰肌醇3-激酶/絲氨酸/蘇氨酸激酶B;信號通路;植物多酚;抗腫瘤
石芳, 廖霞, 李瑤, 等. 植物多酚通過PI3K/Akt信號通路抗腫瘤作用研究進展[J]. 食品科學, 2016, 37(15): 259-264.
SHI Fang, LIAO Xia, LI Yao, et al. Plant polyphenols exert anti-tumor activity by the PI3K/Akt signaling pathway: a review[J]. Food Science, 2016, 37(15): 259-264. (in Chinese with English abstract) DOI:10.7506/spkx1002-6630-201615044. http://www.spkx.net.cn
惡性腫瘤是全球三大致死原因之一,嚴重威脅人類健康和生命。統(tǒng)計數(shù)據(jù)顯示,2015年,我國有281.4萬人因惡性腫瘤而死亡,致死率排列前五的分別為肺癌、胃癌、肝癌、食道癌和結(jié)直腸癌[1]。許多研究表明,腫瘤的發(fā)生與發(fā)展是多因素、多基因、多途徑的結(jié)果,而細胞信號轉(zhuǎn)導途徑在腫瘤的發(fā)生發(fā)展、侵襲轉(zhuǎn)移過程中至關(guān)重要。其中磷脂酰肌醇3-激酶/絲氨酸/蘇氨酸激酶B(phosphatidylinositol 3-kinase/serine/threonine kinase B,PI3K/Akt)信號通路在調(diào)控實體腫瘤(如肝癌[2]、乳腺癌[3]、結(jié)腸癌[4]、胃癌[5]、黑 色素瘤[6]、神經(jīng)母細胞瘤[7])和血液腫瘤(如白血?。?])中發(fā)揮著重要作用。PI3K/Akt信號通路是細胞內(nèi)一條重要的信號轉(zhuǎn)導通路,PI3K作為聯(lián)系胞外信號與細胞應答效應的橋梁分子,在一系列上游或旁路信號分子的影響下,作用于下游的多種效應分子,從而促進細胞侵襲遷移、抑制細胞凋亡、加速細胞周期進程、促進細胞增殖。明確該信號通路在體內(nèi)的作用機制,尋找阻斷該信號通路的靶向藥物是國內(nèi)外研究熱點之一。
植物化 學物質(zhì)的抗腫瘤活性已被廣泛認可,尤其是植物多酚,具有安全有效、來源廣泛的特點,是一類極具應用前景的天然抗 腫瘤藥物。因此,通過PI3K/Akt信號通路抗腫瘤的作用機制來了解植物多酚,有助于開發(fā)植物多酚類抗腫瘤保健食品或藥物。
1.1PI3K/Akt的結(jié)構(gòu)與功能
PI3K為脂質(zhì)激酶家族成員,是一種可特異性催化磷脂酰肌醇磷酸化產(chǎn)生3,4,5-三磷酸磷脂酰肌醇的激酶,分為3 個亞型(I、II、III)。I型PI3K是由催化亞基與調(diào)節(jié)亞基組成的異二聚體,催化亞基由p110α、p110β、p110γ和p110δ組成,基因編碼分別是PIK3CA、PIK3CB、PIK3CG和PIK3CD。調(diào)節(jié)亞基由p85α、p85β和p55γ組成,基因編碼分別是PIK3R1、PIK3R2、PIK3R3[9]。II型PI3K以磷脂酰肌醇(phosphatid ylinositol,PI)及磷脂酰肌醇磷酸(phosphatidylinositol phosphate,PIP)為底物,從N端到C端依次排列著富含脯氨酸區(qū)、Ras結(jié)合區(qū)、HR區(qū)、PX結(jié)構(gòu)域和C2結(jié)構(gòu)域[10]。III型PI3K為酵母空泡蛋白分選同源物,由調(diào)節(jié)亞基pl50和豆蔻?;拇呋瘉喕鵳100組成異二聚體,在細胞內(nèi)以PI為底物,并與自噬、吞噬、溶酶體分類和細胞信號轉(zhuǎn)導作用密切相關(guān)[11]。PI3K參與細胞增殖、抑制細胞凋亡、細胞遷移、膜泡轉(zhuǎn)運、血管生成、細胞癌性轉(zhuǎn)化等過程,并通過由其催化形成的3-磷酸肌醇脂分子(PIP、PIP2、PIP3)起作用。
Akt為蛋白激酶B(protein kinase B,PKB),是分子質(zhì)量為57 kD的絲/蘇氨酸蛋白激酶,含有480 個氨基酸殘基,與蛋白激酶A(68%的同源性)和蛋白激酶C(73%的同源性)具有同源性。Akt激酶與腺苷酸/鳥苷酸(adenosine monophosphate/guanosine monophosphate,AMP/GMP)激酶和蛋白激酶C同屬于ACG蛋白激酶家族。PKB家族已分離出三個成員,分別為PKBα(Akt1)、PKBβ(Akt2)和PKBγ(Akt3)。它們的氨基酸同源性達80%以上,而且都具有3 個相同的結(jié)構(gòu)區(qū)域:氨基末端的血小板-白細胞C激酶底物同源(pleckstrin homology,PH)結(jié)構(gòu)區(qū)域、Akt分子中心區(qū)的激酶活性區(qū)和羧基末端的調(diào)節(jié)區(qū)。PH區(qū)域廣泛存在于信號蛋白和細胞骨架相關(guān)蛋白中,可以介導蛋白質(zhì)和脂質(zhì)、蛋白質(zhì)和蛋白質(zhì)之間的相互作用。
1.2PI3K/Akt的活化與調(diào)節(jié)
PI3K的激活(圖1)可通過與受體酪氨酸激酶(receptor tyrosine kinase,RTK)和G蛋白連接受體相互作用,也可通過Ras蛋白與其p110亞基直接結(jié)合而被激活[12-13]。結(jié)果是在質(zhì)膜上產(chǎn)生PIP3,PIP3招募具有PH結(jié)構(gòu)域的信號蛋白到質(zhì)膜上,包括磷酸肌醇依賴性蛋白激酶1(phosphoinositide-dependent kinase-1,PDK1)和Akt,使得Akt構(gòu)象發(fā)生變化,導致激活Akt所必需的兩個重要磷酸化位點(蘇氨酸(threonine,Thr)308和絲氨酸(serine,Ser)473)暴露。這樣就可由整合素偶聯(lián)激酶(integrin linked kinase,ILK)、DNA依賴蛋白激酶(DNA-dependent protein kinase,DNA-PK)、哺乳動物雷帕霉素靶蛋白(the mammalian target of rapamyein,mTOR)或Akt本身所激活[14]?;罨驛kt離開細胞膜進入細胞核發(fā)揮作用,進一步引起其他蛋白磷酸 化,包括雷帕霉素靶蛋白復合體1(mammalian target of rapamycin complex 1,mTORC1)、糖原合成激酶3(glycogen synthase kinase 3,GSK3)、叉頭轉(zhuǎn)錄因子(forkhead transcription factors,F(xiàn)OXO)、腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)等,從而調(diào)節(jié)細胞蛋白的合成、細胞生長、增殖擴散、存活 以及新陳代謝等活動[15-20]。
PI3K/Akt信號通路受多種因子的調(diào)節(jié),參與PI3K/Akt信號通路的調(diào)節(jié)因子主要有類脂磷酸酶(如,phosphatase and tensin homolog deleted on chromosome ten,(PTEN))、SHIP2(SH2-containing inositol 5-phosphatase,SHIP2)和C末端調(diào)節(jié)蛋白(carboxylterminal modulator protein,CTMP)等負調(diào)節(jié)因子。PTEN是多種細胞生長、分化和維持生存的抑制物,具有蛋白磷酸酶活性和脂質(zhì)磷酸酶活性,從PIP3的3位脫磷酸而將其轉(zhuǎn)變?yōu)镻I(4,5)P2,使PIP3維持在較低的水平,從而阻斷Akt及其下游效應分子的有效活化[21],PTEN活性喪失可導致PI3K/Akt通路永久激活。Akca等[22]發(fā)現(xiàn)PTEN的失活可促進PI3K/Ak t/核因子κB(nuclear factor κB,NF-κB)通路活化,并進一步導致肺癌細胞的侵襲能力增強。CTMP是一種線粒體蛋白,在線粒體內(nèi)裂解后轉(zhuǎn)化為功能蛋白,與Akt羧基端調(diào)節(jié)區(qū)結(jié)合,抑制Akt的磷酸化,從而阻斷下游信號傳導。SHIP2是一種磷酸酯酶,可對PIP3進行5位去除磷酸,將其轉(zhuǎn)變成PI(3,4)P2而降解,進而使其喪失功能[21]。
圖1 PI3K/Akt信號通路激活機制[1133]Fig. 1 Mechanism of PI3K/Akt signaling pathway activation[13]
2.1PI3K/Akt信號通路抑制腫瘤細胞停滯和凋亡
目前認為PI3K/Akt信號通路調(diào)控細胞凋亡主要通過以下幾個途徑[13,23]:1)B細胞淋巴瘤/白血病-2基因(B-cell lymphoma-2,Bcl-2)家族中磷酸化的促凋亡分子蛋白(Bcl-2/ Bcl-xl associated death promoter,Bad)與抗凋亡因子Bcl-xl或Bcl-2解聚,Bad與 抗凋亡結(jié)合蛋白14-3-3相結(jié)合,而Bcl-xl或Bcl-2發(fā)揮抑制細胞凋亡的作用;此外,PI3K/Akt通路的激活也可以使Bcl-2相關(guān)X蛋白(Bcl-2 associated X protein,Bax)的Ser184殘基磷酸化而使其失活,從而抑制細胞凋亡;2)通過磷酸化蛋白水解酶Caspase-9的Ser196位點而使之失活,進一步抑制線粒體釋放細胞色素c及凋亡因子,抑制細胞凋亡;3)調(diào)控轉(zhuǎn)錄因子的表達。叉頭轉(zhuǎn)錄因子(forkhead-type transcription factors,F(xiàn)KHR)可被Akt直接磷酸化,不能進入細胞核抑制抗凋亡因子Fas-L的轉(zhuǎn)錄,從而抑制細胞凋亡;4)磷酸化鼠雙微染色體2(murine double mimute2,MDM2)。Akt磷酸化MDM2的Ser166和Ser188位點后,下調(diào)凋亡蛋白p53,抑制細胞周期停滯和細胞凋亡。
2.2PI3K/Akt信號通路促進腫瘤細胞生存和增殖
活化的Akt可調(diào)節(jié)多種與細胞增殖相關(guān)的蛋白(如mTOR、原癌基因等),促進細胞增殖,具體如下:1)磷酸化mTOR。mTOR是Akt信號最重要的下游因子,可調(diào)節(jié)翻譯過程中關(guān)鍵因子的表達,如核糖體蛋白S6激酶(ribosomal S6 kinase,RSK)和翻譯抑制因子4E-結(jié)合蛋白1(4E-binding protein1, 4E-BP1)等,促進腫瘤細胞增殖。2)Akt能夠直接或間接調(diào)節(jié)磷酸化激活κB激酶(inhibitor of nuclear factor kappa-B kinase,IKK)的活性,導致NF-κB的抑制劑IκB發(fā)生降解,使NF-κB從細胞質(zhì)中釋放出來轉(zhuǎn)移至核內(nèi),激活其靶基因而促進細胞的存活;3)Akt通過使GSK3激酶磷酸化失活,阻止細胞周期蛋白D1和腫瘤蛋白Myc的降解,上調(diào)細胞周期素依賴性激酶-4(cyclin dependent kinase 4,CDK4),或者磷酸化細胞周期素依賴性激酶(cyclin dependent kinase,CDK)的抑制因子P21和P27,從而失去對細胞周期的抑制性調(diào)控作用,加速細胞周期進程,促進細胞增殖[24]。
2.3PI3K/Akt信號通路促進腫瘤細胞侵襲和轉(zhuǎn)移
PI3K/Akt信號通路在腫瘤細胞遷移中起著重要作用。腫瘤上皮細胞間充質(zhì)轉(zhuǎn)分化(epithelial-mesenchymal transition,EMT)與腫瘤細胞侵襲、遷移等生物學行為密切相關(guān)。PI3K/Akt信號通路通過上調(diào)核轉(zhuǎn)錄因子Snail、Slug等,抑制細胞內(nèi)E-鈣黏蛋白的表達[25]或通過上調(diào)基質(zhì)金屬蛋白酶(matrix metalloproteinase,MMP),促進MMP對E-鈣黏蛋白的降解,直接誘導EMT,增強細胞的運動能力和侵襲能力[26]。在對鱗狀細胞癌(head and neck squamous cell carcinoma,HNSCC)的研究中發(fā)現(xiàn),表皮生長因子(epidermal growth factor,EGF)激活表皮生長因子受體(epithelial growth factor receptor,EGFR)后,誘導EMT表型改變以及MMP9介導的E-鈣黏蛋白的降解,激活PI3K信號通路,促進細胞侵襲、遷移[27]。
隨著人們對PI3K/Akt信號通路的認識不斷深入,許多研究者試圖利用多種方法尋找阻斷該信號轉(zhuǎn)導通路的靶向藥物,如基因敲除[28]、RNA干擾[29]以及化學藥物阻斷[30]等,以預防腫瘤的發(fā)生。而植物多酚的抗腫瘤活性已被廣泛認可,大量研究證實,許多植物多酚(如白藜蘆醇、姜黃素、原花青素、表沒食子兒茶素沒食子酸酯、槲皮素等)可以通過干擾PI3K/Akt信號通路(圖2),直接抑制PI3K或阻斷PI3K/Akt信號通路,進一步調(diào)節(jié)其下游效應分子的表達,從而加速腫瘤細胞周期、促進細胞凋亡和抑制細胞增殖,達到抗腫瘤的作用[31]。
圖2 植物多酚通過PI3K/Akt信號通路抗腫瘤作用機制[3311]Fig. 2 Anti-tumor mechanism of plant polyphenols through the PI3K/Akt signaling pathway[31]
3.1白藜蘆醇
白藜蘆醇是廣泛存在于葡萄等植物中的多酚化合物,對多種腫瘤細胞都有一定的抗癌活性。白藜蘆醇通過抑制PI3K/Akt/mTOR信號通路,下調(diào)下游分子p70S6K和4E-BP1的磷酸化,同時激活Caspase-3,增加細胞周期蛋白D1表達水平,加速細胞周期,抑制人慢性粒細胞白血病K562細胞的增殖,誘導其凋亡。進一步研究發(fā)現(xiàn),PI3K和Akt的選擇抑制劑LY294002可與白藜蘆醇發(fā)揮協(xié)同作用[32]。白藜蘆醇還可通過抑制PI3K/Akt/NF-κB信號轉(zhuǎn)導通路,下調(diào)基質(zhì)金屬蛋白酶MMP-2表達,阻止惡性膠質(zhì)瘤起始細胞(glioblastoma-initiating cells,GICs)的侵襲和轉(zhuǎn)移[33]。Zhang Dequan等[34]用白藜蘆醇處理永生性大鼠肝星狀細胞(the immortalized rat hepatic stellate cells,t-HSC/CI-6)后,發(fā)現(xiàn)細胞內(nèi)Toll樣本受體4(toll like receptor 4,TLR4)、PI3K和Akt表達下降,從而阻斷了TLR4介導的NF-κB的轉(zhuǎn)導,抑制肝星狀細胞的激活,表明白藜蘆醇通過阻斷PI3K/Akt信號通路而產(chǎn)生抑制癌細胞作用。
3.2姜黃素
姜黃素是一種從姜黃等根莖中提取的多酚類色素,通過調(diào)節(jié)細胞周期,促進細胞凋亡,抑制細胞增殖而發(fā)揮抗腫瘤作用,被稱作第三代腫瘤化學預防劑。已有研究證實姜黃素通過調(diào)控PI3K/Akt信號通路而具有抗癌活性,其作用機制是姜黃素使Akt去磷酸化,抑制叉頭轉(zhuǎn)錄因子FOXO磷酸化,導致細胞周期相關(guān)蛋白p21和p27Kip表達下降,從而減緩腫瘤的發(fā)展[35]。Zhang Hao等[36]用姜黃素處理腎癌細胞(the renal cell carcinoma,RCC)-949時還發(fā)現(xiàn),姜黃素能夠上調(diào)Bcl-2、下調(diào)Bax的表達,降低細胞周期蛋白B1的表達量,在G2/M期啟動細胞周期停滯,抑制細胞增殖,促進細胞凋亡。Liu Hao等[37]研究姜黃素衍生物(T63)誘導肺癌細胞A549的作用機制時發(fā)現(xiàn),T63不僅可以通過阻滯細胞周期蛋白p21、p27和細胞周期蛋白D1,使細胞凋亡,而且還能夠上調(diào)蛋白磷酸酶2A(protein phosphatase 2A,PP2A)蛋白,抑制Akt磷酸化,從而激活FOXO3a和Bad,促進細胞色素c釋放,激活Caspase-3,誘導細胞凋亡。
3.3原花青素
原花青素是由不同數(shù)量的兒茶素或表兒茶素結(jié)合而成的多酚類物質(zhì),具有抗乳腺癌、前列腺癌、直腸癌等作用。有研究發(fā)現(xiàn),原花青素六聚體(hexamer,Hex)可以降低結(jié)直腸癌發(fā)生,hex可以促進線粒體中細胞色素c釋放到細胞質(zhì),抑制Caco-2細胞PI3K/Akt信號通路,下調(diào)下游蛋白Bad、GSK-3β的表達,誘導細胞凋亡[38]。葡萄籽原花青素(proanthocyanidins from grape seeds,GSPs)也可通過抑制PI3K/Akt信號通路,下調(diào)Bcl-2和Bcl-xl表達,上調(diào)Bax表達,同時激活Caspase-3,誘導人胰腺癌細胞(Miapaca-2、PANC-1和AsPC-1))凋亡[39]。Prasad等[40]發(fā)現(xiàn)蔓越莓原花青素(cranberry-derived proanthocyanidin,C-PAC)誘導食管腺癌細胞(esophageal adenocarcinoma,EAC)的凋亡與PI3K/Akt通路失活有關(guān),也與促凋亡蛋白(Bax、Bak1、脫酰胺Bcl-xl、細胞色素c)、MAPKs的表達及G2/M周期阻滯有關(guān)。
3.4表沒食子兒茶素沒食子酸酯(epigallocatechin gallate,EGCG)
EGCG是綠茶中含量最豐富的成分之一。綠茶的抗癌作用大多數(shù)是通過EGCG介導的。EGCG通過磷酸化Akt,抑制Bad磷酸化,上調(diào)Bax和Bad表達,下調(diào)Bcl-2表達,誘導細胞色素c、Caspase-9和細胞凋亡因子釋放,進而促進膀胱癌移行性細胞株凋亡[41]。EGCG還可通過影響PI3K/Akt信號通路的多種效應分子發(fā)揮抗腫瘤作用,如下調(diào)COX-2、同時激活Caspase-3和Caspase-9,誘導肝癌細胞凋亡、抑制MMP-2和MMP-9活性,發(fā)揮抗腫瘤細胞轉(zhuǎn)移的作用[42-43]、介導PI3K/Akt/mTOR信號通路,促進B淋巴瘤細胞凋亡[44]、下調(diào)PI3K、Akt、NF-κB的表達水平,使肝癌細胞SMMC7721在S期停滯,誘導細胞凋亡[45]。
3.5槲皮素
槲皮素是一種黃酮類化合物,對多種惡性腫瘤具有預防和治療作用。槲皮素的抗癌作用主要是通過結(jié)合PI3K,抑制Akt磷酸化,上調(diào)p53的表達,調(diào)控Bax和Bcl-2的表達來誘導癌細胞的凋亡,阻止細胞的遷移和侵襲,抑制癌細胞的增殖[46-48]。槲皮素還可通過影響PI3K/Akt通路,并增強NF-κB核轉(zhuǎn)位,降低Bcl-x1/Bal的比值,上調(diào)抑癌基因Bim和凋亡誘導因子(apoptosisinducing factor,AIF)表達,起到抑制黑色素瘤細胞B16F10的作用[49]。Xiang Tao等[50]研究也證實槲皮素誘導HeLa細胞凋亡是通過下調(diào)PI3K/Akt信號通路中PI3K、Akt和Bcl-2表達,上調(diào)Bax表達,使細胞在G0/G1細胞周期阻滯。Wang Piwen等[51]的研究還發(fā)現(xiàn)槲皮素和牛蒡子苷元對抑制前列腺癌細胞增殖具有協(xié)同作用,也是通過抑制PI3K/Akt信號通路而起作用的。
3.6其他
還有許多植物多酚類化合物通過調(diào)控PI3K/Akt信號通路而應用于腫瘤治療。例如,芹菜素作為ATP競爭抑制劑,阻斷PI3K的ATP結(jié)合位點,并且抑制與細胞增殖相關(guān)的Akt及其下游促凋亡蛋白Bad的磷酸化,從而抑制PI3K/Akt信號通路發(fā)揮其抗腫瘤作用[52]。熊果酸通過調(diào)控PI3K/Akt信號通路的Bcl-2、Bcl-xl、凋亡抑制基因Survivin、p-mTOR的表達,激活Caspase-3,抑制細胞增殖,誘導細胞凋亡,顯著抑制前列腺腫瘤細胞LNCaP的生長[53]。
PI3K/Akt信號通路是一條經(jīng)典的抑制細胞凋亡、促進細胞增殖的信號轉(zhuǎn)導通路,與多種腫瘤的發(fā)生、侵襲、轉(zhuǎn)移等過程密切相關(guān)。植物多酚是一類廣泛存在于食物中的天然化合物,具有良好的預防腫瘤的作用。越來越多的研究發(fā)現(xiàn)植物多酚可作用于PI3K/Akt信號通路,調(diào)節(jié)其相應基因或蛋白的表達,發(fā)揮抑制細胞凋亡、促進細胞增殖的作用從而降低癌癥的發(fā)生。植物多酚除通過PI3K/Akt信號傳導通路發(fā)揮抗腫瘤作用外,還可以通過MAPK、核轉(zhuǎn)錄相關(guān)因子2(NF-E2-related factor 2,
Nrf2)等細胞信號通路達到抗腫瘤作用。因此,還需深入研究植物多酚抗腫瘤作用機制,為挖掘植物多酚抗腫瘤活性功能,開發(fā)植物多酚類抗腫瘤保健食品或藥物提供依據(jù)。
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Plant Polyphenols Exert Anti-Tumor Activity by the PI3K/Akt Signaling Pathway: A Review
SHI Fang1, LIAO Xia1, LI Yao1, LI Yao1, XIAO Xingning1, WU Surui2, MING Jian1,2,3,*
(1. College of Food Science, Southwest University, Chongqing 400715, China; 2. Kunming Edible Fungi Institute, All China Federation of Supply and Marketing Cooperatives, Kunming 650223, China; 3. Chongqing Engineering Research Center of Regional Food, Chongqing 400715, China)
The phosphatidylinositol 3-kinase/serine/threonine kinase B (PI3K/Akt) signaling pathway is a classical signaling pathway that inhibits apoptosis and promotes proliferation. The PI3K/Akt pathway play an important role in cancer,cardiovascular disease, diabetes and nervous system diseases, especially in cancer. The abnormal activation of PI3K/Akt is closely related to the occurrence, invasion and metastasis of tumors. The research of this pathway has become the focus of the treatment of cancer at home and abroad. Plant polyphenols are becoming natural drugs to prevent cancer because of their anti-tumor effect. This review outlines the structure and activation mechanism of the PI3K/Akt signaling pathway and its relationship with tumor in order to provide scientific evidence for the development of plant polyphenols into health foods or drugs for cancer prevention.
phosphatidylinositol 3-kinase/serine/threonine kinase B (PI3K/Akt); signaling pathway; plant polyphenols; antitumor activity
10.7506/spkx1002-6630-201615044
Q964.8;R151.2
A
1002-6630(2016)15-0259-06
10.7506/spkx1002-6630-201615044. http://www.spkx.net.cn
2016-04-02
國家自然科學基金面上項目(31471576);重慶市社會民生科技創(chuàng)新專項(cstc2015shmszx80019);“十二五”國家科技支撐計劃項目(2013BAD16B01)
石芳(1993—),女,碩士研究生,研究方向為食品化學與營養(yǎng)學。E-mail:1107982769@qq.com
明建(1972—),男,教授,博士,研究方向為食品化學與營養(yǎng)學。E-mail:mingjian1972@163.com
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