EP4 通过磷脂酰肌醇 3 激酶/蛋白激酶 B 信号通路介导前列腺素 E2 依赖性细胞存活。
EP4 mediates PGE2 dependent cell survival through the PI3 kinase/AKT pathway.
作者信息
George Robert J, Sturmoski Mark A, Anant Shrikant, Houchen Courtney W
机构信息
Washington University School of Medicine, Department of Internal Medicine, St. Louis, Missouri 63110, USA.
出版信息
Prostaglandins Other Lipid Mediat. 2007 Feb;83(1-2):112-20. doi: 10.1016/j.prostaglandins.2006.10.005. Epub 2007 Jan 3.
Abstract
The anti-apoptotic effect of PGE(2) was examined in Jurkat cells (human T-cell leukemia) by incubation with PGE(2) (5 nM) prior to treatment with the cancer chemotherapeutic agent camptothecin. Apoptosis was evaluated by caspase-3 activity in cell extracts and flow cytometry of propidium iodide-labeled cells. Pre-incubation with PGE(2) reduced camptothecin-induced caspase activity by 30% and apoptosis by 35%, respectively. Pharmacological data demonstrate that the EP4 receptor is responsible for mediating the protection from camptothecin-induced apoptosis. Pre-treatment of the cells with the EP4 antagonist (EP4A) prior to PGE(2) and camptothecin abolished the increased survival effect of PGE(2). Specific inhibition of the downstream of PI3 kinase or AKT/protein kinase but not protein kinase A prevents the observed increase in cell survival elicited by PGE(2). These findings have critical implications regarding the mechanism and potential application of PGE(2) receptor specific inhibition in cancer therapy.
摘要
在人T细胞白血病Jurkat细胞中，通过在癌症化疗药物喜树碱处理前用PGE(2)（5 nM）孵育来检测PGE(2)的抗凋亡作用。通过细胞提取物中的caspase-3活性以及碘化丙啶标记细胞的流式细胞术评估细胞凋亡。与PGE(2)预孵育分别使喜树碱诱导的caspase活性降低30%，细胞凋亡降低35%。药理学数据表明，EP4受体负责介导对喜树碱诱导凋亡的保护作用。在PGE(2)和喜树碱之前用EP4拮抗剂（EP4A）预处理细胞消除了PGE(2)增加的存活效应。PI3激酶或AKT/蛋白激酶下游的特异性抑制而非蛋白激酶A可阻止观察到的由PGE(2)引起的细胞存活增加。这些发现对于PGE(2)受体特异性抑制在癌症治疗中的机制和潜在应用具有关键意义。
相似文献
1
EP4 mediates PGE2 dependent cell survival through the PI3 kinase/AKT pathway.EP4 通过磷脂酰肌醇 3 激酶/蛋白激酶 B 信号通路介导前列腺素 E2 依赖性细胞存活。
Prostaglandins Other Lipid Mediat. 2007 Feb;83(1-2):112-20. doi: 10.1016/j.prostaglandins.2006.10.005. Epub 2007 Jan 3.
2
Prostaglandin E2 promotes lung cancer cell migration via EP4-betaArrestin1-c-Src signalsome.前列腺素 E2 通过 EP4-β-arrestin1-c-Src 信号小体促进肺癌细胞迁移。
Mol Cancer Res. 2010 Apr;8(4):569-77. doi: 10.1158/1541-7786.MCR-09-0511. Epub 2010 Mar 30.
3
Prostaglandin E2 stimulates human lung carcinoma cell growth through induction of integrin-linked kinase: the involvement of EP4 and Sp1.前列腺素E2通过诱导整合素连接激酶刺激人肺癌细胞生长：EP4和Sp1的参与
Cancer Res. 2009 Feb 1;69(3):896-904. doi: 10.1158/0008-5472.CAN-08-2677. Epub 2009 Jan 27.
4
EP2 and EP4 receptors differentially mediate MAPK pathways underlying anabolic actions of prostaglandin E2 on bone formation in rat calvaria cell cultures.EP2和EP4受体以不同方式介导丝裂原活化蛋白激酶（MAPK）信号通路，该信号通路是前列腺素E2对大鼠颅骨细胞培养物中骨形成产生合成代谢作用的基础。
Bone. 2009 Jun;44(6):1177-85. doi: 10.1016/j.bone.2009.02.010. Epub 2009 Feb 21.
5
Insulin inhibits caspase-3 activity in human renal tubular epithelial cells via the PI3-kinase/Akt pathway.胰岛素通过PI3激酶/Akt信号通路抑制人肾小管上皮细胞中半胱天冬酶-3的活性。
Cell Physiol Biochem. 2008;21(4):279-86. doi: 10.1159/000129386. Epub 2008 Apr 23.
6
Prostaglandin E(2) promotes cell proliferation via protein kinase C/extracellular signal regulated kinase pathway-dependent induction of c-Myc expression in human esophageal squamous cell carcinoma cells.前列腺素E(2)通过蛋白激酶C/细胞外信号调节激酶途径依赖的c-Myc表达诱导促进人食管鳞状细胞癌细胞增殖。
Int J Cancer. 2009 Dec 1;125(11):2540-6. doi: 10.1002/ijc.24607.
7
Prostaglandin (PG) FP and EP1 receptors mediate PGF2alpha and PGE2 regulation of interleukin-1beta expression in Leydig cell progenitors.前列腺素（PG）FP和EP1受体介导前列腺素F2α和前列腺素E2对睾丸间质细胞祖细胞中白细胞介素-1β表达的调节。
Endocrinology. 2003 Apr;144(4):1284-91. doi: 10.1210/en.2002-220868.
8
Hypertonicity stimulates PGE2 signaling in the renal medulla by promoting EP3 and EP4 receptor expression.高渗性通过促进EP3和EP4受体表达来刺激肾髓质中的前列腺素E2信号传导。
Kidney Int. 2009 Feb;75(3):278-84. doi: 10.1038/ki.2008.498. Epub 2008 Oct 8.
9
Selective inhibition of prostaglandin E2 receptors EP2 and EP4 induces apoptosis of human endometriotic cells through suppression of ERK1/2, AKT, NFkappaB, and beta-catenin pathways and activation of intrinsic apoptotic mechanisms.前列腺素E2受体EP2和EP4的选择性抑制通过抑制ERK1/2、AKT、NFκB和β-连环蛋白信号通路以及激活内源性凋亡机制诱导人子宫内膜异位细胞凋亡。
Mol Endocrinol. 2009 Aug;23(8):1291-305. doi: 10.1210/me.2009-0017. Epub 2009 Apr 30.
10
Cyclooxygenase-1-derived PGE2 promotes cell motility via the G-protein-coupled EP4 receptor during vertebrate gastrulation.在脊椎动物原肠胚形成过程中，环氧化酶-1衍生的前列腺素E2通过G蛋白偶联的EP4受体促进细胞运动。
Genes Dev. 2006 Jan 1;20(1):77-86. doi: 10.1101/gad.1374506.
引用本文的文献
1
Cancer stem cells induced by chronic stimulation with prostaglandin E2 exhibited constitutively activated PI3K axis.前列腺素 E2 慢性刺激诱导的癌症干细胞表现出持续激活的 PI3K 轴。
Sci Rep. 2022 Sep 17;12(1):15628. doi: 10.1038/s41598-022-19265-7.
2
Inhibition of Cytosolic Phospholipase A2α Induces Apoptosis in Multiple Myeloma Cells.细胞质型磷脂酶 A2α 的抑制诱导多发性骨髓瘤细胞凋亡。
Molecules. 2021 Dec 9;26(24):7447. doi: 10.3390/molecules26247447.
3
Metabolic pathways in obesity-related breast cancer.肥胖相关乳腺癌中的代谢途径。
Nat Rev Endocrinol. 2021 Jun;17(6):350-363. doi: 10.1038/s41574-021-00487-0. Epub 2021 Apr 29.
4
Celecoxib induces apoptosis through Akt inhibition in 5-fluorouracil-resistant gastric cancer cells.塞来昔布通过抑制Akt诱导5-氟尿嘧啶耐药胃癌细胞凋亡。
Toxicol Res. 2020 Apr 27;37(1):25-33. doi: 10.1007/s43188-020-00044-3. eCollection 2021 Jan.
5
A Review of Prostanoid Receptors: Expression, Characterization, Regulation, and Mechanism of Action.前列腺素受体综述：表达、特性、调控及作用机制
J Cell Commun Signal. 2021 Jun;15(2):155-184. doi: 10.1007/s12079-020-00585-0. Epub 2020 Sep 24.
6
Cardiac injury modulates critical components of prostaglandin E signaling during zebrafish heart regeneration.心脏损伤在斑马鱼心脏再生过程中调节前列腺素 E 信号的关键成分。
Sci Rep. 2020 Feb 20;10(1):3095. doi: 10.1038/s41598-020-59868-6.
7
COX2 is induced in the ovarian epithelium during ovulatory wound repair and promotes cell survival†.在排卵性伤口修复过程中，COX2 在卵巢上皮细胞中被诱导产生，并促进细胞存活†。
Biol Reprod. 2019 Nov 21;101(5):961-974. doi: 10.1093/biolre/ioz134.
8
PI3K-AKT-mTOR and NFκB Pathways in Ovarian Cancer: Implications for Targeted Therapeutics.卵巢癌中的PI3K-AKT-mTOR和NFκB信号通路：对靶向治疗的启示
Cancers (Basel). 2019 Jul 5;11(7):949. doi: 10.3390/cancers11070949.
9
Prostaglandin E and an EP4 receptor agonist inhibit LPS-Induced monocyte chemotactic protein 5 production and secretion in mouse cardiac fibroblasts via Akt and NF-κB signaling.前列腺素 E 和 EP4 受体激动剂通过 Akt 和 NF-κB 信号通路抑制 LPS 诱导的小鼠心肌成纤维细胞单核细胞趋化蛋白 5 的产生和分泌。
Prostaglandins Other Lipid Mediat. 2019 Oct;144:106349. doi: 10.1016/j.prostaglandins.2019.106349. Epub 2019 Jun 20.
10
An ARC-Regulated IL1β/Cox-2/PGE2/β-Catenin/ARC Circuit Controls Leukemia-Microenvironment Interactions and Confers Drug Resistance in AML.一个由 ARC 调控的 IL1β/Cox-2/PGE2/β-Catenin/ARC 回路控制白血病微环境相互作用，并赋予 AML 耐药性。
Cancer Res. 2019 Mar 15;79(6):1165-1177. doi: 10.1158/0008-5472.CAN-18-0921. Epub 2019 Jan 23.
本文引用的文献
1
Mitochondrial dysfunction and oxidative stress as determinants of cell death/survival in stroke.线粒体功能障碍和氧化应激作为中风中细胞死亡/存活的决定因素。
Ann N Y Acad Sci. 2005 May;1042:203-9. doi: 10.1196/annals.1338.022.
2
The activation of Akt/PKB signaling pathway and cell survival.Akt/PKB信号通路的激活与细胞存活。
J Cell Mol Med. 2005 Jan-Mar;9(1):59-71. doi: 10.1111/j.1582-4934.2005.tb00337.x.
3
Prostaglandin E2 reduces radiation-induced epithelial apoptosis through a mechanism involving AKT activation and bax translocation.前列腺素E2通过一种涉及AKT激活和bax易位的机制减少辐射诱导的上皮细胞凋亡。
J Clin Invest. 2004 Dec;114(11):1676-85. doi: 10.1172/JCI22218.
4
Prostaglandin E2 promotes the survival of bone marrow-derived dendritic cells.前列腺素E2可促进骨髓来源的树突状细胞存活。
J Immunol. 2004 Dec 1;173(11):6955-64. doi: 10.4049/jimmunol.173.11.6955.
5
Mechanism of prostaglandin (PG)E2-induced prolactin expression in human T cells: cooperation of two PGE2 receptor subtypes, E-prostanoid (EP) 3 and EP4, via calcium- and cyclic adenosine 5'-monophosphate-mediated signaling pathways.前列腺素（PG）E2诱导人T细胞中催乳素表达的机制：两种前列腺素E2受体亚型，即前列腺素E受体（EP）3和EP4，通过钙和环磷酸腺苷介导的信号通路协同作用。
J Immunol. 2004 Nov 15;173(10):5952-62. doi: 10.4049/jimmunol.173.10.5952.
6
Prostaglandin EP receptors: targets for treatment and prevention of colorectal cancer?前列腺素EP受体：治疗和预防结直肠癌的靶点？
Mol Cancer Ther. 2004 Aug;3(8):1031-9.
7
Inhibition of apoptosis in normal and transformed intestinal epithelial cells by cAMP through induction of inhibitor of apoptosis protein (IAP)-2.环磷酸腺苷（cAMP）通过诱导凋亡抑制蛋白（IAP）-2来抑制正常和转化的肠上皮细胞中的细胞凋亡。
Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8921-6. doi: 10.1073/pnas.1533221100. Epub 2003 Jul 1.
8
Prostaglandin E2 protects gastric mucosal cells from apoptosis via EP2 and EP4 receptor activation.前列腺素E2通过激活EP2和EP4受体保护胃黏膜细胞免于凋亡。
J Biol Chem. 2003 Apr 11;278(15):12752-8. doi: 10.1074/jbc.M212097200. Epub 2003 Jan 29.
9
Autocrine/paracrine regulation of apoptosis in epithelial cells by prostaglandin E2.前列腺素E2对上皮细胞凋亡的自分泌/旁分泌调节
Prostaglandins Leukot Essent Fatty Acids. 2002 Nov;67(5):357-63. doi: 10.1054/plef.2002.0442.
10
Prosurvival and antiapoptotic effects of PGE2 in radiation injury are mediated by EP2 receptor in intestine.前列腺素E2在辐射损伤中的促生存和抗凋亡作用由肠道中的EP2受体介导。
Am J Physiol Gastrointest Liver Physiol. 2003 Mar;284(3):G490-8. doi: 10.1152/ajpgi.00240.2002. Epub 2002 Nov 13.
Zotero 插件