Pioglitazone inhibits the proliferation and metastasis of human pancreatic cancer cells

Ninomiya,Itasu; Yamazaki,Keisuke; Oyama,Katsunobu; Hayashi,Hironori; Tajima,Hidehiro; Kitagawa,Hirohisa; Fushida,Sachio; Fujimura,Takashi; Ohta,Tetsuo

doi:10.3892/ol.2014.2553

Pioglitazone inhibits the proliferation and metastasis of human pancreatic cancer cells

Authors:
- Itasu Ninomiya
- Keisuke Yamazaki
- Katsunobu Oyama
- Hironori Hayashi
- Hidehiro Tajima
- Hirohisa Kitagawa
- Sachio Fushida
- Takashi Fujimura
- Tetsuo Ohta
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Affiliations: Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan
Published online on: September 23, 2014 https://doi.org/10.3892/ol.2014.2553
Pages: 2709-2714

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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 lines in vitro. Pioglitazone induced CEA mRNA expression, suppressed IL‑8 and COX‑2 mRNA expression in 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.

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