Adrenomedullin antagonist suppresses in vivo growth of human pancreatic cancer cells in SCID mice by suppressing angiogenesis.

Takahisa Ishikawa, Jian Chen, Jingxin Wang, Futoshi Okada, Toshiro Sugiyama, Takahiko Kobayashi, Masanobu Shindo, Fumihiro Higashino, Hiroyuki Katoh, Masahiro Asaka, Takeshi Kondo, Masuo Hosokawa, Masanobu Kobayashi

Index: Oncogene 22 , 1238-1242, (2003)

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Abstract

Since it is reported that adrenomedullin (AM) upregulated by hypoxia inhibits hypoxic cell death, we examined the effects of AM antagonist (AM C-terminal fragment; AM(22-52)) on the growth of pancreatic cancer cells. We, for the first time, demonstrated that AM antagonist significantly reduced the in vivo growth of the pancreatic cancer cell line. Immunohistochemical analysis demonstrated that the mean diameter of blood vessels was significantly smaller in the tumor tissues treated with AM antagonist than in those treated with AM N-terminal fragment (AM(1-25)), and that the PCNA-labeling index was lower in the former than in the latter. Then we demonstrated that AM antagonist showed no effect on the in vitro growth of the pancreatic cancer cell line. These results showed that AM played an important role in the growth of pancreatic cancer cells in vivo, suggesting that AM antagonist might be a useful tool for treating pancreatic cancers.