title: Pioglitazone inhibits the proliferation and metastasis of human pancreatic cancer cells.
abstract: Proliferator-activated receptor-γ (PPAR-γ) is a nuclear receptor that acts as a transcription factor in several types of tissue. PPAR-γ ligands are known to inhibit numerous cancer cell processes, including pancreatic cancer cell proliferation through terminal differentiation. Previous studies concerning the inhibitory effect of PPAR-γ ligands derived from thiazolidinediones (TZDs) on the metastatic potential of cancer cells have been reported. The present study aimed to investigate whether pioglitazone, a prescription TZD class drug and a ligand of PPAR-γ, inhibits the proliferation and metastasis of pancreatic cancer cells. The inhibitory effect of pioglitazone on the proliferation of the Capan-1, Aspc-1, BxPC-3, PANC-1 and MIApaCa-2 pancreatic cancer cell lines was analyzed. Alterations in carcinoembryonic antigen (CEA), interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2) mRNA expression levels subsequent to pioglitazone treatment were examined in BxPC-3 cells by quantitative reverse transcription polymerase chain reaction. In addition, whether the oral administration of pioglitazone prevents tumorigenesis and spontaneous BxPC-3 cell lymph node and lung metastases was investigated using a rectal xenograft model. Pioglitazone treatment resulted in the inhibition of proliferation in all five pancreatic cancer cell linesin vitro. Pioglitazone induced CEA mRNA expression, suppressed IL-8 and COX-2 mRNA expressionin vitro, and inhibited BxPC-3 xenograft growth. Pioglitazone also reduced BxPC-3 cell lymph node and lung metastasis in the rectal xenograft model. These results suggest that pioglitazone treatment inhibited the proliferation and metastasis of pancreatic cancer cells through the induction of differentiation and the inhibition of angiogenesis-associated protein expression.
authors.affiliation: Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Itasu
authors.initials: I
authors.lastname: Ninomiya
authors.affiliation: Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Katsunobu
authors.initials: K
authors.lastname: Oyama
authors.affiliation: Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Tajima
authors.affiliation: Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kitagawa
authors.affiliation: Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Fushida
authors.affiliation: Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohta
keywords: differentiation; lung metastasis; lymph node metastasis; pancreatic cancer; pioglitazone; rectal xenograft model