Pigment epithelium-derived factor inhibits lysosomal degradation of Bcl-xL and apoptosis in HepG2 cells.
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.
Kawaguchi
Takumi
T
Department of Digestive Disease Information and Research, Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. takumi@med.kurume-u.ac.jp
Yamagishi
Sho-Ichi
S
Itou
Minoru
M
Okuda
Koji
K
Sumie
Shuji
S
Kuromatsu
Ryoko
R
Sakata
Masahiro
M
Abe
Mitsuhiko
M
Taniguchi
Eitaro
E
Koga
Hironori
H
Harada
Masaru
M
Ueno
Takato
T
Sata
Michio
M
D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D021983:Cyclophilins / Q000235:genetics / Q000378:metabolism; D003720:Densitometry; D005136:Eye Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D018942:Macrolides / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015843:Serpins / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
D002166:Camptothecin; D021983:Cyclophilins; D005136:Eye Proteins; D007976:Leupeptins; D018942:Macrolides; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015843:Serpins; D051020:bcl-X Protein; D000099174:Pigment Epithelium-Derived Factor; C040929:bafilomycin A1; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde