磷酯酰肌醇-3激酶/蛋白激酶B（PI3K/Akt）信号通路是肿瘤、炎症等发生发展过程中一条重要的信号通路。研究发现，在许多肿瘤组织中，PI3K/Akt信号通路过度表达和活化与肿瘤的进展密切相关。上游分子通过与PI3K结合，使其构象发生改变，从而磷酸化激活Akt，Akt的活化能调控其下游分子，参与肿瘤调控通路。近年来，PI3K/Akt信号通路在肿瘤中的重要作用受到众多学者的关注，多种肿瘤组织中检测到PI3K/Akt信号通路的过度活化，因此靶向该信号通路的研究成为研究热点。目前关于靶向PI3K/Akt信号通路的抗肿瘤药物在肿瘤治疗方面的临床试验已经展开，Wortmannin、LY294002等PI3K/Akt信号通路抑制剂有着广阔的临床应用前景。

[1] ENGELMAN J A,LUO J,CANTLEY L C,et al.The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism[J].Nat Rev Genet,2006,7:606-619.
[2] ODA K,STOKOE D,TAKETANI Y,et al.High frequency of coexistent mutations of PIK3CA and PTEN genes inendometrial carcinoma[J].Cancer Res,2005,65(23):10669-10673.
[3] SHAW R J,CANTLEY L C.Ras,PI(3) K and mTOR signaling controls tumour cell growth[J].Nature,2006,441(7092):424-430.
[4] KATSO R,OKKENHAUG K,AHMADI K,et al.Cellular function of phosphoinositide 3-kinases:implications for development,homeostasis,and cancer[J].Annu Rev Cell Dev Biol,2001,17:615-675.
[5] ZHAO L,VOGT P K.Class I PI3K in oncogenic cellular transformation[J].Oncogene,2008,27(41):5486-5496.
[6] LEE H T,KAY E P.Regulatory role of cAMP on expression of Cdk4 and p27(Kip1) by inhibiting phosphatidylionositol 3-kinase in corneal endothelial cells[J].Invest Ophthalmol Vis Sci,2003,44(9):3816-3825.
[7] MAIRA S M,FINAN P,GARCIA-ECHEVERRIA C.From the bench to the bed side:PI3K pathway inhibitors in clinical development[J].Curr Top Microbiol Immunol,2010,347:209-239.
[8] WARD S G,FINAN P.Isoform-specific phosphoinesitide 3-kinase inhibitors as therapeutic agents[J].Current Opinion In Phammaology,2003,3(4):426-434.
[9] ENGELMAN J A,LUO J,CANTLEY L C.The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism[J].Nat Rev Genet,2006,7:606-619.
[10] SHI F,WANG Y C,ZHAO T Z,et al.Effects of simulated microgravity on human umbilical vein endothelial cell angiogenesis and role of the PI3K-Akt-eNOS signal Pathway[J].PLoS ONE,2012,7(7):e40365.
[11] SONG G,OUYANG G L,BAO S D.The activation of Akt/PKB signaling pathway and cell survival[J].Cell Mol Med,2005,9(1):59-71.
[12] XIN M,DENG X.Nicotine in activation of the proapoptotic function of bax through phosphorylation[J].J Biol Chem,2005,280(11):10781-10789.
[13] MANNING B D,CANTLEY L C.AKT/PKB signaling:navigating downstream[J].Cell,2007,129(7):1261-1274.
[14] BURGERING B M,MEDEMA R H.Decisions on life and death:FOXO forkhead transcription factorsare in command when PKB/Akt is off duty[J].J Leukoc Biol,2003,73(6):689-701.
[15] 常立功,黄培林.mTOR信号通路与大肠癌演进相关性的研究进展[J].东南大学学报:医学版,2013,32(2):243-247.
[16] YOUSIF N G.Fibronectin promotes migration and invasion of ovarian cancer cells through up-regulation of FAK-PI3K/Akt pathway[J].Cell Biol Int,2014,38(1):85-91.
[17] CHEN Y,WANG Z,CHANG P,et al.The effect of focal adhesion kinase gene silencing on 5-fluorouracil chenosensitivitu involves an Akt/NF-kappaB signling pathway in colorectal carcrinomas[J].Int J Cancer,2010,127(1):195-206.
[18] XU Z Z,XIA Z G,WANG A H,et al.Activation of the PI3K/AKT/mTOR pathway in diffuse large B cell lymphoma:clinical significance and inhibitory effect of rituximab[J].Ann Hematol,2013,92(10):1351-1358.
[19] RIPKA S,NEESSE A,RIEDEL J,et al.CUX1:target of Akt signaling ang mediator of resisitance to apoptosis in pancreatic cancer[J].Gut,2010,59(8):1101-1110.
[20] CUMBERBATCH M,TANG X,BERAN G,et al.Identification of a subset of human non-small cell lung cancer patients with high PI3Kbeta and low PTEN expression,more prevalent in SCC[J].Clin Cancer Res,2013,11:27.
[21] XIE X,TANG B,ZHOU J,et al.Inhibition of the PI3K/Akt pathway increases the chemosensitivity of gastric cancer to vincristine[J].Oncol Rep,2013,30(2):773-782.
[22] ZHANG Y,YAO X,JIANG C,et al.Expression of PI3K,PTEN and Akt in small intestinal adenocarcinoma detected by quantum dots-based immunofluorescence technology[J].Cancer Biomark,2013,13(4):299-305.
[23] YOTHAISONG S,DOKDUANG H,TECHASEN A,et al.Increased activation of PI3K/AKT signaling pathway is associated with cholangiocarcinoma metastasis and PI3K/mTOR inhibition presents a possible therapeutic strategy[J].Tumour Biol,2013,34(6):3637-3648.
[24] UEGAK K,KANAMORI Y,KIGAWA J,et al.PTEN-positive and phosphorylated-Akt-negafive expression is a predictor of survival for patients with advanced endometrial carcmoma[J].Oncol Rep,2005,14(2):389-392.
[25] 张劲远,张银旭,张俊华.PI3K/Akt信号通路对人大肠癌hct-8/FU耐药细胞P-GP表达和耐药性的影响[J].东南大学学报院:医学版,2013,32(2):169-172.
[26] ELFIKY A A,AZIZ S A.Characterization and targeting of phosphatidylinositol-3 kinase(PI3K) and mammalian target of rapamycin(mTOR) in renal[J].J Transl Med,2011,9:133.
[27] LEUNG E,KIM J E,REWCASTLE G W,et al.Comparison of the effects of the PI3K/mTOR inhibitors NVP-BEZ235 and GSK2126458 on tamoxifen-resistant breast cancer cells[J].Cancer Biology & Therapy,2011,11(11):938-946.
[28] OHTA T,OHMICHI M,HAYASAKA T,et al.Inhibition of phosphatidylinositol-3-kinase increases efficacy of cisplatin in in vivo ovarian cancer models[J].Endocrinology,2006,147(4):1761-1769.
[29] WORKMAN P,CLARKE P A,RAYNAUD F I,et al.Drugging the PI3 kinome:from chemical tools to drugs in the clinic[J].Cancer Res,2010,70(6):2146-2157.
[30] KNIGHT S D,ADAMS N D,BURGESS J L,et al.Discovery of GSK2126458,a highly potent inhibitor of PI3K and the mammalian target of rapamycin[J].Acs Med Chem Lett,2010,1(1):39-43.
[31] ADHAMI V M,SYED D N,KHAN N,et al.Dietary flavonoid fisetin:a novel dual inhibitor of PI3K/Akt and mTOR for prostate cancer management[J].Biochem Pharmacol,2012,84(10):1277-1281.
[32] AHMAD A,BIERSACK B,LI Y,et al.Deregulation of PI3K/Akt/mTOR signaling pathways by isoflavones and its implication in cancer treatment[J].Anticancer Agents Med Chem,2013,13(7):1014-1024.