Activation of peroxisome proliferator-activated receptor gamma inhibits the growth of human pancreatic cancer.
OBJECTIVE
In the present study, we examined the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in human pancreatic cancer and the possible effects of its ligand engagement on cell growth.


METHODS
Seven human pancreatic cancer cell lines and 7 surgically resected human pancreatic cancer tissues were used as samples. The expression of PPARgamma was analyzed with reverse transcription-polymerase chain reaction and immunoblotting. The interaction between PPARgamma and PPAR-responsive element (PPRE) was examined by gel shift assay. Growth inhibition by thiazolidinediones was confirmed with anchorage-dependent and anchorage-independent growth assays.


RESULTS
PPARgamma was detected in all cell lines tested and in 5 out of 7 cancer tissues (71%), but was not found in adjacent normal pancreatic tissues. Gel shift analysis revealed that the proteins in nuclear extracts of the pancreatic cancer cell line PANC-1 specifically bind to the PPRE. Cell growth was significantly inhibited by treatment with troglitazone and rosiglitazone in a dose- and time-dependent manner (p < 0.01). In contrast, a nonfunctional metabolic analog of troglitazone did not affect cell growth.


CONCLUSIONS
These observations suggest that PPARgamma plays an important role in human pancreatic cancer growth and that ligand-induced activation of PPARgamma would be a useful strategy for treatment of human pancreatic cancer.
Sasaki
T
T
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan. tamito@hiroshima-u.ac.jp
Fujimoto
Y
Y
Tsuchida
A
A
Kawasaki
Y
Y
Kuwada
Y
Y
Chayama
K
K
D000970:Antineoplastic Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D000077288:Troglitazone; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D002839:Chromans; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D000077288:Troglitazone