Regular Articles
Pigment Epithelium-Derived Factor Inhibits Lysosomal Degradation of Bcl-xL and Apoptosis in HepG2 cells

https://doi.org/10.2353/ajpath.2010.090242Get rights and content
Under an Elsevier user license
open archive

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 lines 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.

Cited by (0)

Supported in part by the Vehicle Racing Commemorative Foundation, a Grant-in-Aid for Young Scientists (number 19790643 to T.K.) and a Grant-in-Aid for Scientific Research (number 21590865 to M.S.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, by Health and Labour Sciences Research Grants for Research on Hepatitis from the Ministry of Health, Labour, and Welfare of Japan, and by a Grant for Cancer Research from Fukuoka Cancer Society.

Supplemental material for this article can be found on http://ajp.amjpathol.org.