新型抑制剂 NVP-AUY922 通过靶向 HSP90 减少胰腺癌的生长和血管生成。
Targeting HSP90 by the novel inhibitor NVP-AUY922 reduces growth and angiogenesis of pancreatic cancer.
机构信息
Department of Surgery, University of Regensburg Medical Center, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany.
出版信息
Anticancer Res. 2012 Jul;32(7):2551-61.
AIM
To evaluate the impact of heat-shock protein 90 (HSP90) blockade by the novel inhibitor NVP-AUY922, on tumor growth and angiogenesis in pancreatic cancer.
MATERIALS AND METHODS
Effects of NVP-AUY922 on signaling pathways were evaluated by western blotting. Cell motility of cancer cells, pericytes and endothelial cells was investigated in Boyden chambers. Impact of HSP90 blockade on pancreatic tumor growth and angiogenesis were studied in in vivo tumor models.
RESULTS
NVP-AUY922 effectively inhibited cancer cell growth. Moreover, HSP90 inhibition potently interfered with multiple signaling pathways in cancer cells, as well as endothelial cells and pericytes, leading to significant reduction of pro-migratory and invasive properties of these cell types. In vivo, treatment with NVP-AUY922 significantly inhibited growth and vascularization of pancreatic cancer at doses far below the maximum tolerated dose.
CONCLUSION
HSP90 blockade by the novel synthetic inhibitor NVP-AUY922 effectively reduces pancreatic cancer progression through direct effects on cancer cells, as well as on endothelial cells and pericytes.
目的
评估新型热休克蛋白 90（HSP90）抑制剂 NVP-AUY922 对胰腺癌肿瘤生长和血管生成的影响。
材料和方法
通过 Western blot 评估 NVP-AUY922 对信号通路的影响。在 Boyden 室中研究癌细胞、周细胞和内皮细胞的迁移能力。在体内肿瘤模型中研究 HSP90 阻断对胰腺肿瘤生长和血管生成的影响。
结果
NVP-AUY922 能有效抑制癌细胞生长。此外，HSP90 抑制可显著干扰癌细胞以及内皮细胞和周细胞中的多种信号通路，导致这些细胞类型的促迁移和侵袭特性显著降低。体内实验表明，NVP-AUY922 在远远低于最大耐受剂量的剂量下可显著抑制胰腺癌的生长和血管生成。
结论
新型合成抑制剂 NVP-AUY922 通过对癌细胞以及内皮细胞和周细胞的直接作用，有效抑制 HSP90 阻断，从而降低胰腺癌的进展。
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