谷胱甘肽过氧化物酶3（GPx3）在肝细胞癌中的临床意义及治疗价值

Clinical significance and therapeutic value of glutathione peroxidase 3 (GPx3) in hepatocellular carcinoma.

作者信息

Qi Xiang, Ng Kevin Tak Pan, Lian Qi Zhou, Liu Xiao Bing, Li Chang Xian, Geng Wei, Ling Chang Chun, Ma Yuen Yuen, Yeung Wai Ho, Tu Wen Wei, Fan Sheung Tat, Lo Chung Mau, Man Kwan

机构信息

Department of Surgery, Centre for Cancer Research, The University of Hong Kong, Pokfulam, Hong Kong, China.

Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.

出版信息

Oncotarget. 2014 Nov 30;5(22):11103-20. doi: 10.18632/oncotarget.2549.

AIMS

We aimed to investigate the clinical significance of GPx3 in hepatocellular carcinoma (HCC) and to characterize its tumor suppressive role.

METHODS

HCC patients (113) who underwent hepatectomy were recruited to examine the clinical relevance of GPx3. The tumor suppressive role of GPx3 was studied by administration of recombinant GPx3 (rGPx3) or over-expression of GPx3 in HCC cells in vitro and in vivo. The therapeutic value of GPx3 for HCC was further investigated using human induced pluripotent stem cell derived mesenchymal stem cells (hiPSC-MSCs) as its delivery vehicle.

RESULTS

Down-regulation of GPx3 significantly correlated with advanced tumor stage (P = 0.024), venous infiltration (P = 0.043) and poor overall survival (P = 0.007) after hepatectomy. Lower plasma GPx3 in HCC patients was significantly associated with larger tumor size (P = 0.011), more tumor nodules (P = 0.032) and higher recurrence (P = 0.016). Over-expression of GPx3 or administration of rGPx3 significantly inhibited proliferation and invasiveness of HCC cells in vitro and in vivo. Tumor suppressive activity of GPx3 was mediated through Erk-NFκB-SIP1 pathway. GPx3 could be delivered by hiPSC-MSCs into the tumor and exhibited tumor suppressive activity in vivo.

CONCLUSIONS

GPx3 is a tumor suppressor gene in HCC and may possess prognostic and therapeutic value for HCC patients.

目的

我们旨在研究谷胱甘肽过氧化物酶3（GPx3）在肝细胞癌（HCC）中的临床意义，并阐明其肿瘤抑制作用。

方法

招募113例行肝切除术的HCC患者，以检测GPx3的临床相关性。通过在体外和体内给予重组GPx3（rGPx3）或在HCC细胞中过表达GPx3，研究GPx3的肿瘤抑制作用。使用人诱导多能干细胞衍生的间充质干细胞（hiPSC-MSCs）作为其递送载体，进一步研究GPx3对HCC的治疗价值。

结果

肝切除术后，GPx3的下调与肿瘤晚期（P = 0.024）、静脉浸润（P = 0.043）及总体生存率差（P = 0.007）显著相关。HCC患者较低的血浆GPx3水平与肿瘤体积较大（P = 0.011）、肿瘤结节较多（P = 0.032）及复发率较高（P = 0.016）显著相关。GPx3的过表达或rGPx3的给予在体外和体内均显著抑制HCC细胞的增殖和侵袭性。GPx3的肿瘤抑制活性通过Erk-NFκB-SIP1途径介导。GPx3可通过hiPSC-MSCs递送至肿瘤，并在体内表现出肿瘤抑制活性。