Celecoxib suppresses hepatoma stemness and progression by up-regulating PTEN

نویسندگان

  • Tian-Huei Chu
  • Hoi-Hung Chan
  • Hsiao-Mei Kuo
  • Li-Fen Liu
  • Tsung-Hui Hu
  • Cheuk-Kwan Sun
  • Mei-Lang Kung
  • Shih-Wei Lin
  • E-Ming Wang
  • Yi-Ling Ma
  • Kwan-Hung Cheng
  • Kwok Hung Lai
  • Zhi-Hong Wen
  • Ping-I Hsu
  • Ming-Hong Tai
چکیده

Celecoxib, a COX-2 inhibitor and non-steroidal anti-inflammatory drug, can prevent several types of cancer, including hepatocellular carcinoma (HCC). Here we show that celecoxib suppressed the self-renewal and drug-pumping functions in HCC cells. Besides, celecoxib depleted CD44+/CD133+ hepatic cancer stem cells (hCSC). Prostaglandin E2 (PGE2) and CD133 overexpression did not reverse the celecoxib-induced depletion of hCSC. Also, celecoxib inhibited progression of rat Novikoff hepatoma. Moreover, a 60-day celecoxib program increased the survival rate of rats with hepatoma. Histological analysis revealed that celecoxib therapy reduced the abundance of CD44+/CD133+ hCSCs in hepatoma tissues. Besides, the hCSCs depletion was associated with elevated apoptosis and blunted proliferation and angiogenesis in hepatoma. Celecoxib therapy activated peroxisome proliferator-activated receptor γ (PPARγ) and up-regulated PTEN, thereby inhibiting Akt and disrupting hCSC expansion. PTEN gene delivery by adenovirus reduced CD44/CD133 expression in vitro and hepatoma formation in vivo. This study suggests that celecoxib suppresses cancer stemness and progression of HCC via activation of PPARγ/PTEN signaling.

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عنوان ژورنال:

دوره 5  شماره 

صفحات  -

تاریخ انتشار 2014