The oncogenic Golgi phosphoprotein 3 like overexpression is associated with cisplatin resistance in ovarian carcinoma and activating the NF-κB signaling pathway.
The oncogenic Golgi phosphoprotein 3 like overexpression is associated with cisplatin resistance in ovarian carcinoma and activating the NF-κB signaling pathway.
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致癌性高尔基体磷蛋白 3 样过度表达与卵巢癌顺铂耐药并激活 NF-κ B 信号通路相关
DOI：
10.1186/s13046-017-0607-0
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发表时间：
2017-10-04
期刊：
影响因子：
--
通讯作者：
Shen H
中科院分区：
文献类型：
--
作者：
He S;Niu G;Shang J;Deng Y;Wan Z;Zhang C;You Z;Shen H
化疗耐药是卵巢癌患者肿瘤复发和治疗失败的主要原因。确定克服耐药性的有效策略将对该疾病产生重大的临床影响。采用Real-time PCR和Western blot分别检测GOLPH3L蛋白和mRNA在卵巢癌细胞系和患者组织中的表达。采用免疫组化法分析177例人卵巢癌组织样本，探讨GOLPH3L表达与卵巢癌患者临床病理特征的关系。功能测定，如MTT、FACS和Tunel测定，用于确定GOLPH3L在人卵巢癌进展中的致癌作用。利用western blotting和荧光素酶法研究GOLPH3L促进卵巢癌细胞化疗耐药的机制。GOLPH3L在卵巢癌细胞系和组织中的表达明显上调，高表达与卵巢癌患者的侵袭性表型和不良预后相关。GOLPH3L过表达赋予卵巢癌细胞CDDP抗性然而，在体外和体内，抑制GOLPH3L使卵巢癌细胞系对CDDP细胞毒性增敏。此外，GOLPH3L上调核p65水平，磷酸化核因子κ b激酶-β和i -κB α抑制剂，从而激活典型核因子-κB （NF-κB）信号传导。我们的研究结果表明，GOLPH3L是卵巢癌治疗的潜在治疗靶点：靶向GOLPH3L信号传导可能是一种有希望的策略，可以增强化疗耐药卵巢癌患者的铂反应。本文的在线版本（10.1186/s13046-017-0607-0）包含补充内容，仅供授权用户使用。
Chemo-resistance is a leading cause of tumor relapse and treatment failure in patients with ovarian cancer. The identification of effective strategies to overcome drug resistance will have a significant clinical impact on the disease. The protein and mRNA expression of GOLPH3L in ovarian cancer cell lines and patient tissues were determined using Real-time PCR and Western blot, respectively. 177 human ovarian cancer tissue samples were analyzed by IHC to investigate the association between GOLPH3L expression and the clinicopathological characteristics of ovarian cancer patients. Functional assays, such as MTT, FACS, and Tunel assay used to determine the oncogenic role of GOLPH3L in human ovarian cancer progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of GOLPH3L promotes chemoresistance in ovarian cancer cells. The expression of GOLPH3L was markedly upregulated in ovarian cancer cell lines and tissues, and high GOLPH3L expression was associated with an aggressive phenotype and poor prognosis with ovarian cancer patients. GOLPH3L overexpression confers CDDP resistance on ovarian cancer cells; however, inhibition of GOLPH3L sensitized ovarian cancer cell lines to CDDP cytotoxicity both in vitro and in vivo. Additionally, GOLPH3L upregulated the levels of nuclear p65 and phosphorylated inhibitor of nuclear factor Kappa-B kinase-β and IκBα, thereby activating canonical nuclear factor-κB (NF-κB) signaling. Our findings suggest that GOLPH3L is a potential therapeutic target for the treatment of ovarian cancer: targeting GOLPH3L signaling may represent a promising strategy to enhance platinum response in patients with chemoresistant ovarian cancer. The online version of this article (10.1186/s13046-017-0607-0) contains supplementary material, which is available to authorized users.
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影响因子：
64.8
作者：
Ponder, BAJ
通讯作者：
Ponder, BAJ
影响因子：
16
作者：
Campbell, KJ;Rocha, S;Perkins, ND
通讯作者：
Perkins, ND
高尔基体磷蛋白 3 (GOLPH3) 通过激活 NF-κB 通路促进肝细胞癌细胞侵袭性
影响因子：
7.3
作者：
Dai, Ting;Zhang, Dongsheng;Song, Libing
通讯作者：
Song, Libing
DOI：
10.1016/s0889-8588(05)70229-x
发表时间：
2001-06-01
影响因子：
2.4
作者：
DiPaola, RS;Patel, J;Rafi, MM
通讯作者：
Rafi, MM
影响因子：
4.7
作者：
Kumar, Amanika;Bakkum-Gamez, Jamie N.;Cliby, William A.
通讯作者：
Cliby, William A.