10Z‑Hymenialdisine inhibits angiogenesis by suppressing NF‑κB activation in pancreatic cancer cell lines

10Z‑Hymenialdisine 通过抑制胰腺癌细胞系中的 NF‑κB 活化来抑制血管生成

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作者:Goro Ueda, Yoichi Matsuo, Hiromichi Murase, Yoshinaga Aoyama, Tomokatsu Kato, Kan Omi, Yuichi Hayashi, Hiroyuki Imafuji, Kenta Saito, Ken Tsuboi, Mamoru Morimoto, Ryo Ogawa, Hiroki Takahashi, Akira Mitsui, Masahiro Kimura, Shuji Takiguchi

Abstract

10Z‑Hymenialdisine is a natural product derived from the marine sponge Axinella carteri. 10Z‑Hymenialdisine has anti‑inflammatory effects exerted through NF‑κB; however, it is unclear whether 10Z‑Hymenialdisine has anti‑angiogenic effects in cancer cells. In the present study, both the anti‑angiogenic and antimetastatic effects of this compound in pancreatic cancer were investigated. It was initially confirmed that 10Z‑Hymenialdisine significantly inhibited the proliferation of pancreatic cancer cells. Next, using both reverse transcription‑quantitative PCR and ELISA, it was demonstrated that 10Z‑Hymenialdisine significantly suppressed the expression of VEGF and IL‑8 mRNAs and proteins in pancreatic cancer. Immunohistochemical analysis revealed that 10Z‑Hymenialdisine inhibited NF‑κB activity in pancreatic cancer cell lines. It was also identified that 10Z‑Hymenialdisine inhibited tube formation in EA.hy926 cells. In vivo, 10Z‑Hymenialdisine significantly inhibited the growth of BxPC‑3 pancreatic cancer cells that were subcutaneously injected into model mice. In conclusion, the present study demonstrated that 10Z‑Hymenialdisine exerted anti‑angiogenic effects by suppressing NF‑κB activity and angiogenic factors, such as VEGF and IL‑8, in pancreatic cancer cell lines. 10Z‑Hymenialdisine has potential applications as a novel therapeutic agent for the treatment of pancreatic cancer.

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