Growth of T-cell lymphoma cells is inhibited by mPGES-1/PGE2 suppression via JAK/STAT, TGF-β/Smad3 and PI3K/AKT signal pathways.
Growth of T-cell lymphoma cells is inhibited by mPGES-1/PGE2 suppression via JAK/STAT, TGF-β/Smad3 and PI3K/AKT signal pathways.
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T 细胞淋巴瘤细胞的生长通过 JAK/STAT、TGF-β/Smad3 和 PI3K/AKT 信号通路受到 mPGES-1/PGE2 抑制的抑制
DOI：
10.21037/tcr-21-2834
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发表时间：
2022-07
影响因子：
0.9
通讯作者：
中科院分区：
文献类型：
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作者：
T细胞淋巴瘤（TCL）预后极差，治疗选择有限，迫切需要新的治疗靶点。本课题组前期研究发现，抑制膜结合型前列腺素E2合成酶1/前列腺素E2（mPGES-1/PGE 2）可通过抑制AKT信号通路发挥抗白血病细胞的作用。本文旨在探讨mPGES-1/PGE 2信号通路在TCL中的作用及其机制。Western blot和免疫荧光检测mPGES-1在TCL细胞系Hut 78中的表达。用mPGES-1选择性抑制剂CAY 10526处理Hut 78细胞。通过使用细胞计数试剂盒-8（CCK-8）进行细胞活力测定。流式细胞仪检测细胞凋亡率。酶免疫分析法（EIA）检测PGE 2的合成。Western blot检测CAY 10526作用后Hut 78细胞mPGES-1、切割型caspase-3、Janus激酶/信号转导和转录（JAK/STAT）、转化生长因子-β（TGF-β）/Smad 3和磷脂酰肌醇3-激酶/蛋白激酶B（PI 3 K/AKT）信号通路的表达。mPGES-1在Hut 78细胞中的表达高于正常外周血单核细胞。CAY 10526抑制Hut 78细胞增殖并诱导其凋亡。这些作用可能部分归因于Caspase家族的激活和JAK/STAT、TGF-β/Smad 3和PI 3 K/AKT信号通路的抑制。我们的结果表明mPGES-1/PGE 2可能是TCL的潜在治疗靶点。
T-cell lymphoma (TCL) has a very poor prognosis with limited treatment options and novel therapeutic target is urgently needed. Our previous studies have found that suppression of membrane-bound prostaglandin E2 synthase l/prostaglandin E2 (mPGES-1/PGE2) exerted anti-neoplastic effects in leukemia cells by suppressing AKT signal pathway. Here, we aim at evaluating the role and mechanism of mPGES-1/PGE2 signaling in TCL. Expression of mPGES-1 in TCL cell line Hut78 was analyzed by Western blot and immunofluorescence. CAY10526, a selective mPGES-1 inhibitor, was used to treat Hut 78 cells. Cell viability assays was performed by using cell counting kit-8 (CCK-8). Cell apoptosis rate was examined by flow cytometer. PGE2 synthesis was detected by enzyme immunoassay (EIA). The expression of mPGES-1, cleaved caspase-3, Janus kinase/signal transduction and transcription (JAK/STAT), transforming growth factor-β (TGF-β)/Smad3 and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway of Hut 78 cells after exposed to CAY10526 was analyzed by Western blot. mPGES-1 was highly expressed in Hut78 cell compared to normal peripheral blood mono-nuclear cells. CAY10526 inhibited cell proliferation and induced apoptosis in Hut78 cells. These effects may be partially attributed to the activation of the Caspase family and the inhibition of JAK/STAT, TGF-β/Smad3 and PI3K/AKT signal pathways. Our results suggested that mPGES-1/PGE2 could be a potential therapeutic target for TCL.
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影响因子：
2.9
作者：
Ghione P;Moskowitz AJ;De Paola NEK;Horwitz SM;Ruella M
通讯作者：
Ruella M
影响因子：
3.8
作者：
Nandi P;Girish GV;Majumder M;Xin X;Tutunea-Fatan E;Lala PK
通讯作者：
Lala PK
影响因子：
6.6
作者：
Banning, Antje;Florian, Simone;Brigelius-Flohe, Regina
通讯作者：
Brigelius-Flohe, Regina
影响因子：
2.7
作者：
Li, Yi-Qing;Chen, Jiao-Ting;Ma, Li-Ping
通讯作者：
Ma, Li-Ping
DOI：
10.12659/msm.906442
发表时间：
2018-04-10
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Sui G;Cheng G;Yuan J;Hou X;Kong X;Niu H
通讯作者：
Niu H