Expression and function of transforming growth factor‑β‑activated protein kinase 1 in gastric cancer.
Expression and function of transforming growth factor‑β‑activated protein kinase 1 in gastric cancer.
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DOI：
10.3892/mmr.2017.6998
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发表时间：
2017-09
影响因子：
3.4
通讯作者：
Chen C
中科院分区：
文献类型：
--
作者：
Yang Y;Qiu Y;Tang M;Wu Z;Hu W;Chen C
本研究旨在探讨转化生长因子（transforming growth factor，TGF）-β-活化蛋白激酶1（transforming growth factor-β-activated protein kinase 1，TAK 1）在胃癌组织中的表达及其意义。采用免疫组化方法检测TAK 1在胃癌手术切除标本及癌旁正常组织中的表达。采用Kaplan-Meier曲线分析TAK 1与临床病理因素的关系，并评价TAK 1表达与总生存率的关系。此外，研究了TAK 1选择性抑制剂5 Z-7-oxozeaenol（OZ）对人胃癌MGC 803细胞体外生物学特性的影响。分别采用细胞增殖实验、流式细胞仪分析和transwell侵袭实验检测TAK 1在胃癌细胞增殖、凋亡和侵袭中的作用。本研究结果表明，胃癌组织和癌旁正常组织中TAK 1的阳性表达率分别为70.5%和25.9%。TAK 1的表达与N分期、病理分期密切相关（P<0.05）。对139例胃癌患者生存分析表明，TAK 1阳性组的总生存率低于TAK 1阴性组（P<0.05）。TAK 1选择性抑制剂OZ处理后，MGC 803细胞的增殖能力和侵袭能力明显降低，磷酸化TAK 1（Thr 187）、核p65、细胞周期蛋白D1、凋亡调节因子Bcl-2和基质金属肽酶（MMP）9的表达水平也明显降低（P<0.05）。OZ处理后MGC 803细胞胞浆细胞色素c和切割型caspase 3的表达水平明显升高，细胞凋亡率明显增加（P<0.05）。总之，这些研究结果表明，增加的TAK 1表达可能参与胃癌的进展，因此，TAK 1可能被用作胃癌治疗的未来治疗靶点。
The present study aimed to investigate the expression and role of transforming growth factor (TGF) -β-activated protein kinase 1 (TAK1) in human gastric cancer. Immunohistochemistry was performed to investigate the expression of TAK1 in surgical specimens of human gastric cancer tissue and adjacent normal tissue. The association between TAK1 and clinicopathologic factors was analyzed and the association between TAK1 expression and the overall survival rates was evaluated using Kaplan-Meier curves. In addition, the effect of the TAK1 selective inhibitor 5Z-7-oxozeaenol (OZ) on the biological characteristics of MGC803 human gastric cancer cells in vitro were investigated. The role of TAK1 in gastric cancer cell proliferation, apoptosis and invasion were determined by cell proliferation assays, flow cytometry analysis and transwell invasion assays, respectively. The findings of the present study demonstrated that the positive expression rate of TAK1 in gastric cancer and adjacent normal tissues was 70.5 and 25.9%, respectively. Furthermore, TAK1 expression was significantly associated with advanced N stage and pathological stage (P<0.05). Survival analysis of 139 patients with gastric cancer indicated a lower overall survival rate of patients in the TAK1-positive group compared with the TAK1-negative group (P<0.05). In addition, treatment with the TAK1 selective inhibitor OZ reduced the proliferation and invasion abilities of MGC803 cells and significantly reduced the expression levels of phosphorylated-TAK1 (Thr187), nuclear p65, cyclin D1, Bcl-2 apoptosis regulator and matrix metallopeptidase (MMP)9 (P<0.05). OZ treatment significantly increased the expression levels of cytosolic cytochrome c and cleaved caspase 3 and the apoptosis rate in MGC803 cells (P<0.05). In conclusion, these findings suggest that increased TAK1 expression may be involved in the progression of gastric cancer; therefore, TAK1 may be used as a future therapeutic target for gastric cancer treatment.
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影响因子：
9
作者：
通讯作者：
--
影响因子：
11.2
作者：
Omori E;Matsumoto K;Zhu S;Smart RC;Ninomiya-Tsuji J
通讯作者：
Ninomiya-Tsuji J
影响因子：
4.3
作者：
Lee, Suk-young;Oh, Sang Cheul
通讯作者：
Oh, Sang Cheul
影响因子：
3.5
作者：
Fakhouri L;El-Elimat T;Hurst DP;Reggio PH;Pearce CJ;Oberlies NH;Croatt MP
通讯作者：
Croatt MP
DOI：
10.1016/j.jcmgh.2017.02.003
发表时间：
2017-05
影响因子：
7.2
作者：
Liu X;Meltzer SJ
通讯作者：
Meltzer SJ