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Medical Oncology

, Volume 23, Issue 3, pp 393–402 | Cite as

Growth inhibition and differentiation induced by peroxisome proliferator activated receptor gamma ligand rosiglitazone in human melanoma cell line A375

  • Yan Li
  • Yang Meng
  • Hongyan Li
  • Jing Li
  • Jianjiang Fu
  • Yue Liu
  • Xiaoguang Chen
Original Article

Abstract

Background

Ligands of peroxisome proliferator-activated receptors (PPARs) have been demonstrated to be antitumorgenic in vitro and in vivo due to their antiproliferative, prodifferential, and antiangiogenic effects. The aim of this study is to evaluate the effects and mechanisms of PPARγ ligand rosiglitazone (ROZ) on the growth, apoptosis, and differentiation in human melanoma cancer cell line A375.

Methods

The effects of ROZ on A375 cell proliferation were measured by clonogenic assay, apoptosis and cell cycle kinietics by FACS with ROZ for 72 h, PPARγ protein was detected by Western blot analysis and immunocytochemical staining, and PPARγ mRNA expression by RT-PCR. The differentiation effect of ROZ was determined by measurement of melanin content and tyrosinase activity. The levels of Bcl-2, P53, p-ERK, and ERK were also detected by Western blot analysis. Inhibition of tumorigensis was observed in nude mice.

Results

ROZ inhibited colony formation and induced apoptosis in A375 cells, and the cells were arrested in G1 phase. This effect was associated with a decrease of the expression of Bcl-2 and increase of the expression of P53. ROZ also induced the differentiation in A375 cells. ROZ increased expression of PPARγ and decreased the expression of ERK and p-ERK. Data in vivo showed that ROZ could inhibit tumorigensis in nude mice.

Conclusion

These results demonstrated that ROZ inhibited growth of A375 cells via the induction of apoptosis, necrosis, and differentiation in a PPARγ-dependent manner and might present a promising therapeutic approach in certain human maligancies.

Key Words

ROZ PPARγ apoptosis differentiation necrosis 

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Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Yan Li
    • 1
  • Yang Meng
    • 1
  • Hongyan Li
    • 1
  • Jing Li
    • 1
  • Jianjiang Fu
    • 1
  • Yue Liu
    • 1
  • Xiaoguang Chen
    • 1
  1. 1.Department of Pharmacology, Institute of Materia MedicaChinese Academy of Medical Sciences & Peking Union Medical CollegeBeijingChina

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