Proteasome inhibitor MG132 inhibits angiogenesis in pancreatic cancer by blocking nf-κb activity

Yoichi Matsuo, Hirozumi Sawai, Nobuo Ochi, Akira Yasuda, Masaki Sakamoto, Hiroki Takahashi, Hitoshi Funahashi, Hiromitsu Takeyama, Sushovan Guha

研究成果: Article査読

31 被引用数 (Scopus)

抄録

Since angiogenesis enables solid tumors, including pancreatic cancer (PaCa), to grow and metastasize, the development of anti-angiogenic agents is currently one of the urgent issues. Proteasome inhibitors are well known for inhibiting nuclear factor-kappa B (NF-κB) activity in various cancer cells, but little is known about their biologic mechanisms against angiogenesis in PaCa. We divided human PaCa cell lines into high-angiogenic (BxPC-3 and SW 1990) and low-angiogenic (MIA PaCa-2 and Capan-2) groups. The high-angiogenic PaCa cell lines constitutively expressed high NF-κB activity and produced high levels of vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8). The conditioned media from BxPC-3 significantly enhanced both proliferation of and tube formation by human umbilical vein endothelial cells (HUVECs) and these enhancements were significantly inhibited by the proteasome inhibitor MG132 treatment. Collectively, MG132 blocked PaCa-derived VEGF and IL-8 production through inhibition of NF-κB activity. Thus, proteasome inhibitors may prove beneficial as anti-angiogenic therapy for PaCa. Our studies show that MG132, a proteasome inhibitor, significantly blocked pancreatic-cancer-associated angiogenesis through inhibition of NF-κB and NF-κB-dependent proangiogenic gene products VEGF and IL-8.

本文言語English
ページ(範囲)1167-1176
ページ数10
ジャーナルDigestive Diseases and Sciences
55
4
DOI
出版ステータスPublished - 04-2010
外部発表はい

All Science Journal Classification (ASJC) codes

  • Physiology
  • Gastroenterology

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