Pigment Epithelium-Derived Factor Inhibits Lysosomal Degradation of Bcl-xL and Apoptosis in HepG2 cells
Pigment Epithelium-Derived Factor Inhibits Lysosomal Degradation of Bcl-xL and Apoptosis in HepG2 cells
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DOI：
10.2353/ajpath.2010.090242
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发表时间：
2010-01-01
影响因子：
6
通讯作者：
Sata, Michio
中科院分区：
文献类型：
--
作者：
Kawaguchi, Takumi;Yamagishi, Sho-ichi;Sata, Michio
色素上皮衍生因子（PEDF）对肿瘤细胞具有多种生物学作用，但其作用具有细胞类型依赖性。本研究的目的是研究PEDF在肝细胞癌（HCC）中的病理生理作用。PEDF表达在各种肝癌细胞系和人HCC组织中进行了检测，并在包括HepG 2细胞在内的各种肝癌细胞细颗粒中观察到。在人HCC组织中，PEDF表达高于邻近的非HCC组织。此外，HCC患者的血清PEDF水平高于非HCC患者，与治疗前水平相比，HCC的根治性治疗导致血清PEDF水平显著降低。在体外实验中，喜树碱（CPT）诱导细胞凋亡和PEDF的影响进行了研究，通过敲低PEDF基因在CPT处理的HepG 2细胞。PEDF基因的敲除增强CPT诱导的细胞凋亡，同时下调HepG 2细胞中Bcl-xL的表达。在PEDF基因敲低的HepG 2细胞中检测凋亡相关分子的表达以及巴弗洛霉素A1对CPT诱导的凋亡的影响。巴弗洛霉素A1处理抑制CPT诱导的Bcl-xL表达减少和PEDF基因敲低的HepG 2细胞凋亡增加。因此，PEDF可以通过抑制CPT处理的HepG 2细胞中Bcl-xL的溶酶体降解来发挥抗凋亡作用。(Am J Pathol 2010，176：168-176; DOI：10.2353/ajpath.2010.090242）
Pigment epithelium-derived factor (PEDF) has several biological actions on tumor cells, but its effects are cell-type dependent. The aim of this study was to examine the pathophysiological role of PEDF in hepatocellular carcinoma (HCC). PEDF expression was examined in various hepatoma cell lines and human HCC tissues, and was seen in various hepatoma cell fines including HepG2 cells. In human HCC tissues, PEDF expression was higher than in adjacent non-HCC tissues. In addition, serum PEDF levels were higher in HCC patients than in non-HCC patients, and curative treatment of HCC caused significant reductions in serum PEDF levels compared with pretreatment levels. In vitro experiments, camptothecin (CPT) was used to induce apoptosis and the effect of PEDF was investigated by knockdown of the PEDF gene in CPT-treated HepG2 cells. Knockdown of the PEDF gene enhanced CPT-induced apoptosis, simultaneously down-regulating Bcl-xL expression in HepG2 cells. Expression of apoptosis-related molecules and effects of bafilomycin A1 on CPT-induced apoptosis were also examined in PEDF gene knockdown HepG2 cells. Treatment with bafilomycin A1 suppressed CPT-induced decreases in Bcl-xL expression and increases in apoptosis in PEDF gene knockdown HepG2 cells. PEDF may, therefore, exert anti-apoptotic effects through inhibition of lysosomal degradation of Bcl-xL in CPT-treated HepG2 cells. (Am J Pathol 2010, 176:168-176; DOI: 10.2353/ajpath.2010.090242)