Antitumor effects of peroxisome proliferator activate receptor gamma ligands on anaplastic thyroid carcinoma.
Anaplastic thyroid carcinoma is an aggressive neoplasm and resistant to all sorts of treatment due to its rapid growth and invasive potential. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor modulating variety of biological properties, such as regulating of adipogenesis, inhibition of cancer cell proliferation or differentiation of tumor cells. The purpose of this study was to evaluate the possibility for the therapeutic effect of PPARgamma ligands against anaplastic thyroid tumor in vitro. Expressions of the PPARc gene and protein were examined in 5 human anaplastic carcinoma cell lines (MSA, IAA, ROA, K119 and KOA-2). We next evaluated the effects of PPARgamma ligands (Thiazolidinedione, Prostaglandin J2 and RS1303) on proliferation, differentiation, apoptosis and invasion. Five cell lines showed higher level of the PPARc gene and protein expression than papillary thyroid carcinoma. PPARgamma ligands inhibited cell proliferation by inducing apoptosis instead of differentiation in dose-dependent manner. PPARgamma ligands also down regulated the invasive potential of 5 cell lines. The inhibitory effect of proliferation or invasion was prominent in 3 cell lines, which exhibited higher expression level of the PPARc gene or protein. Our results indicated that PPARgamma ligands modify malignant potential of anaplastic carcinoma cell lines altering growth or invasive properties, suggesting that PPARgamma could be potentially the novel molecular target for human thyroid anaplastic carcinoma.
Hayashi
Nobuyasu
N
Department of Surgery and Clinical Oncology Graduate School of Medicine, Osaka University, Suita City, Osaka 565-0871, Japan.
Nakamori
Shoji
S
Hiraoka
Nobuaki
N
Tsujie
Masanori
M
Xundi
Xu
X
Takano
Toru
T
Amino
Nobuyuki
N
Sakon
Masato
M
Monden
Morito
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D008024:Ligands; D009361:Neoplasm Invasiveness; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D008024:Ligands; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; C037112:9-deoxy-delta-9-prostaglandin D2; C089946:2,4-thiazolidinedione; D015230:Prostaglandin D2