Apollon modulates chemosensitivity in human esophageal squamous cell carcinoma.
Apollon modulates chemosensitivity in human esophageal squamous cell carcinoma.
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Apollon 调节人食管鳞状细胞癌的化疗敏感性
DOI：
10.18632/oncotarget.2293
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发表时间：
2014-08-30
期刊：
影响因子：
--
通讯作者：
Dong L
中科院分区：
文献类型：
--
作者：
Zhang S;Tang W;Weng S;Liu X;Rao B;Gu J;Chen S;Wang Q;Shen X;Xue R;Dong L
食管鳞状细胞癌（ESCC）患者通常被诊断为晚期疾病，对化疗反应较差。在此我们报道了Apollon，一种膜相关凋亡抑制蛋白，在ESCC细胞系和临床ESCC组织中过表达，Apollon过表达与化疗反应差（P = 0.001）和总生存期短（P = 0.021）相关。Apollon基因敲减增加了顺铂/紫杉醇诱导的两种ESCC细胞系的凋亡、线粒体功能障碍和细胞色素c释放。Apollon基因敲减增强了顺铂/紫杉醇诱导的长期细胞生长抑制，并增强了异种移植肿瘤模型中ESCC细胞对顺铂/多西他赛的化疗敏感性。Apollon敲除还增强了顺铂/紫杉醇诱导的ESCC细胞和异种移植肿瘤模型中caspase-8（外源性途径）和caspase-9（内源性途径）的活化。机制研究表明，Apollon对化疗敏感性的影响主要通过Smac介导。临床ESCC组织中Apollon表达与Smac表达呈强负相关（P = 0.001）。Apollon靶向Smac在ESCC细胞中的降解。Apollon对ESCC细胞化疗敏感性的影响被Smac敲低逆转。总之，我们的数据显示Apollon表达与ESCC的化疗反应相关，并为Apollon拮抗作用与化疗联合治疗ESCC提供了强有力的理论基础。
Patients with esophageal squamous cell carcinoma (ESCC) are often diagnosed with advanced diseases that respond poorly to chemotherapy. Here we reported that Apollon, a membrane-associated inhibitor of apoptosis protein, was overexpressed in ESCC cell lines and clinical ESCC tissues, and Apollon overexpression clinically correlated with poor response to chemotherapy (P = 0.001), and short overall survival (P = 0.021). Apollon knockdown increased cisplatin/docetaxel-induced apoptosis, mitochondrial dysfunction and cytochrome c release in two ESCC cell lines. Apollon knockdown potentiated cisplatin/docetaxel-induced long-term cell growth inhibition, and enhanced chemosensitivity of ESCC cells to cisplatin/docetaxel in xenograft tumor models. Apollon knockdown also enhanced cisplatin/docetaxel-induced activation of caspase-8 (extrinsic pathway) and caspase-9 (intrinsic pathway) in ESCC cells and xenograft tumor models. Mechanism studies revealed that the effect of Apollon on chemosensitivity is mainly mediated by Smac. Apollon expression strongly and negatively correlated with Smac expression in clinical ESCC tissues (P = 0.001). Apollon targeted Smac for degradation in ESCC cells. The effect of Apollon on chemosensitivity was reversed by Smac knockdown in ESCC cells. Taken together, our data show association of Apollon expression with chemotherapeutic response in ESCC, and provide a strong rationale for combining Apollon antagonism with chemotherapy to treat ESCC.
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影响因子：
8.8
作者：
Lopergolo, A.;Pennati, M.;Gandellini, P.;Orlotti, N. I.;Poma, P.;Daidone, M. G.;Folini, M.;Zaffaroni, N.
通讯作者：
Zaffaroni, N.
影响因子：
16
作者：
Bartke, T;Pohl, C;Jentsch, S
通讯作者：
Jentsch, S
DOI：
10.1006/bbrc.1999.1585
发表时间：
1999-11-02
影响因子：
3.1
作者：
Chen, ZH;Naito, M;Tsuruo, T
通讯作者：
Tsuruo, T
影响因子：
5.1
作者：
Chu, L.;Gu, J.;Liu, X.
通讯作者：
Liu, X.
影响因子：
78.5
作者：
Brown, JM;Attardi, LD
通讯作者：
Attardi, LD