Suppression of 14-3-3ζ in cholangiocarcinoma cells inhibits proliferation through attenuated Akt activity, enhancing chemosensitivity to gemcitabine.
Suppression of 14-3-3ζ in cholangiocarcinoma cells inhibits proliferation through attenuated Akt activity, enhancing chemosensitivity to gemcitabine.
复制标题
DOI：
10.3892/ol.2017.7326
复制
发表时间：
2018-01
期刊：
影响因子：
2.9
通讯作者：
Namwat N
中科院分区：
文献类型：
--
作者：
Kittirat Y;Techasen A;Thongchot S;Loilome W;Thanan R;Yongvanit P;Sungkhamanon S;Titapun A;Khuntikeo N;Namwat N
蛋白14-3-3ζ通过与磷酸化的丝氨酸/苏氨酸残基结合，在多种肿瘤中发挥重要的调节作用，促进细胞周期进程、细胞增殖和抗凋亡。本研究旨在探讨14-3-3-ζ在胆管癌细胞发生发展中的作用，阐明14-3-3ζ表达介导的蛋白激酶B(Akt)磷酸化及其化疗敏感性的分子机制。本研究采用免疫组织化学方法检测14-3-3ζ在临床标本中的表达，并与临床病理特征进行比较。用双变量相关分析确定14-3-3-ζ与磷酸化Akt之间的相关性。应用小干扰ζ技术研究14-3-3RNA抑制对颈总动脉细胞功能和吉西他滨敏感性的影响。14-3-3ζ的表达与PAKT呈正相关(P=0.013)，14-3-3ζ和PAKT的高表达与总生存率和转移显著相关(P分别为0.025和0.006)。小干扰RNA下调14-3-3ζ可抑制细胞增殖，从而抑制PACK活性，增加细胞周期抑制因子p27的蛋白水平。抑制14-3-3-ζ可通过诱导细胞凋亡而增强吉西他滨对颈总动脉细胞增殖的抑制作用。综上所述，本研究结果表明14-3-3-ζ是CCA的一个潜在靶点，并可能作为一种新的治疗方法来提高CCA的化疗敏感性。
The protein 14-3-3ζ contributes important regulatory functions in several cellular processes via binding to phosphorylated serine/threonine residues, which promotes cell cycle progression, cell proliferation and anti-apoptosis in multiple types of cancer. The aim of the present study was to investigate the functions of 14-3-3ζ in cholangiocarcinoma (CCA) progression and elucidate the molecular mechanism of 14-3-3ζ expression-mediated protein kinase B (Akt) phosphorylation and chemosensitivity in CCA cells. In the present study, 14-3-3ζ expression was investigated in clinical specimens using immunohistochemistry and compared with the clinicopathological features of patients with CCA. The association between 14-3-3ζ and phosphorylated Akt (pAkt) was determined among the tissues of the same patients using bivariate correlation analysis. The effects of 14-3-3ζ suppression on CCA cell function and gemcitabine sensitivity were investigated using small interfering RNA (siRNA). It was identified that 14-3-3ζ expression was positively correlated with pAkt (P=0.013) and that increased expression of 14-3-3ζ and pAkt were significantly associated with poor overall survival rate and metastasis (P=0.025 and 0.006, respectively). Downregulation of 14-3-3ζ using siRNA in CCA cell lines decreased cell proliferation, resulting in the inhibition of pAkt activity and increasing the protein level of the cell cycle inhibitor p27. The suppression of 14-3-3ζ enhanced the inhibitory effect of gemcitabine on CCA cell proliferation by inducing apoptotic cell death. Taken together, the results of the present study indicated that 14-3-3ζ is a potential target for CCA and may serve as a novel therapeutic approach to enhance chemosensitivity in the treatment of CCA.
登录
查看更多内容
影响因子：
7.3
作者：
Freeman, Alyson K.;Morrison, Deborah K.
通讯作者：
Morrison, Deborah K.
影响因子：
11.2
作者：
Neal CL;Yao J;Yang W;Zhou X;Nguyen NT;Lu J;Danes CG;Guo H;Lan KH;Ensor J;Hittelman W;Hung MC;Yu D
通讯作者：
Yu D
14-3-3zeta的过表达是口腔癌的早期事件。
影响因子：
3.8
作者：
Matta A;Bahadur S;Duggal R;Gupta SD;Ralhan R
通讯作者：
Ralhan R
影响因子：
11.2
作者：
Fan, Tao;Li, Ruiyun;Jiang, Feng
通讯作者：
Jiang, Feng
影响因子：
2.5
作者：
Sripa, Banchob;Pairojkul, Chawalit
通讯作者：
Pairojkul, Chawalit