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Pioglitazone inhibits the proliferation and metastasis of human pancreatic cancer cells.

Ninomiya I, Yamazaki K, Oyama K, Hayashi H, Tajima H, Kitagawa H, Fushida S, Fujimura T, Ohta T - Oncol Lett (2014)

Bottom Line: Proliferator-activated receptor-γ (PPAR-γ) is a nuclear receptor that acts as a transcription factor in several types of tissue.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.

View Article: PubMed Central - PubMed

Affiliation: Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.

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.

No MeSH data available.


Related in: MedlinePlus

Comparison of metastasized tumor cell numbers in para-aortic lymph nodes and lungs of pioglitazone- and vehicle-treated mice bearing BxPC-3 pancreatic cancer cell rectal xenografts. The number of metastasized tumor cells was calculated by amplification of the human β-globin gene and is presented as the number of tumor cells in the organ. Pioglitazone significantly inhibited lymph node and lung metastases (P=0.0357 and P=0.046, respectively; Mann-Whitney U test).
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f3-ol-08-06-2709: Comparison of metastasized tumor cell numbers in para-aortic lymph nodes and lungs of pioglitazone- and vehicle-treated mice bearing BxPC-3 pancreatic cancer cell rectal xenografts. The number of metastasized tumor cells was calculated by amplification of the human β-globin gene and is presented as the number of tumor cells in the organ. Pioglitazone significantly inhibited lymph node and lung metastases (P=0.0357 and P=0.046, respectively; Mann-Whitney U test).

Mentions: Macroscopically, the BxpPC-3 xenograft produced a locally aggressive rectal tumor, and subsequently, lymph node metastases surrounding the abdominal aorta appeared six weeks after tumor cell inoculation. Pioglitazone macroscopically inhibited xenograft growth and abdominal lymph node metastasis. The antitumor activity of pioglitazone in the xenograft was examined by comparing the wet weight of each xenograft, and pioglitazone was found to significantly inhibit BxPC-3 xenograft growth by 82.6% (P=0.046; Table I). The antimetastatic activity of pioglitazone was examined by amplifying the human β-globin-related sequence in the lymph nodes and the lungs of rectal xenograft mice. Quantification of cancer metastasis by calculating the number of metastasized tumor cells using the quantitatively-amplified β-globin gene revealed that pioglitazone significantly inhibited lymph node and lung metastasis (P=0.035 and P=0.046, respectively; Fig. 3; Table II).


Pioglitazone inhibits the proliferation and metastasis of human pancreatic cancer cells.

Ninomiya I, Yamazaki K, Oyama K, Hayashi H, Tajima H, Kitagawa H, Fushida S, Fujimura T, Ohta T - Oncol Lett (2014)

Comparison of metastasized tumor cell numbers in para-aortic lymph nodes and lungs of pioglitazone- and vehicle-treated mice bearing BxPC-3 pancreatic cancer cell rectal xenografts. The number of metastasized tumor cells was calculated by amplification of the human β-globin gene and is presented as the number of tumor cells in the organ. Pioglitazone significantly inhibited lymph node and lung metastases (P=0.0357 and P=0.046, respectively; Mann-Whitney U test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4214501&req=5

f3-ol-08-06-2709: Comparison of metastasized tumor cell numbers in para-aortic lymph nodes and lungs of pioglitazone- and vehicle-treated mice bearing BxPC-3 pancreatic cancer cell rectal xenografts. The number of metastasized tumor cells was calculated by amplification of the human β-globin gene and is presented as the number of tumor cells in the organ. Pioglitazone significantly inhibited lymph node and lung metastases (P=0.0357 and P=0.046, respectively; Mann-Whitney U test).
Mentions: Macroscopically, the BxpPC-3 xenograft produced a locally aggressive rectal tumor, and subsequently, lymph node metastases surrounding the abdominal aorta appeared six weeks after tumor cell inoculation. Pioglitazone macroscopically inhibited xenograft growth and abdominal lymph node metastasis. The antitumor activity of pioglitazone in the xenograft was examined by comparing the wet weight of each xenograft, and pioglitazone was found to significantly inhibit BxPC-3 xenograft growth by 82.6% (P=0.046; Table I). The antimetastatic activity of pioglitazone was examined by amplifying the human β-globin-related sequence in the lymph nodes and the lungs of rectal xenograft mice. Quantification of cancer metastasis by calculating the number of metastasized tumor cells using the quantitatively-amplified β-globin gene revealed that pioglitazone significantly inhibited lymph node and lung metastasis (P=0.035 and P=0.046, respectively; Fig. 3; Table II).

Bottom Line: Proliferator-activated receptor-γ (PPAR-γ) is a nuclear receptor that acts as a transcription factor in several types of tissue.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.

View Article: PubMed Central - PubMed

Affiliation: Gastroenterologic Surgery, Department of Oncology, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa, Japan.

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.

No MeSH data available.


Related in: MedlinePlus