Department of Surgery, Peking University First Hospital, Beijing, 100034, People's Republic of China.
Langenbecks Arch Surg. 2010 Jun;395(5):515-25. doi: 10.1007/s00423-009-0493-9. Epub 2009 Apr 25.
Pancreatic cancer is an aggressive malignancy with a poor prognosis. The overall 5-year survival rate of pancreatic cancer is less than 5%, and has not improved significantly for years. Further understanding of the molecular carcinogenesis of pancreatic cancer is critical for designing effective ways to treat this type of malignancy.
In this study, we examine expression of hedgehog signaling molecules in 54 surgically removed pancreatic cancer specimens as well as seven available pancreatic cancer cell lines.
We find that expression of Ptch is associated with tumor size, tumor differentiation, lymph node metastasis, and clinical stages, whereas expression of Smo is associated with tumor differentiation and lymph node metastasis. Our studies from pancreatic cancer cell lines indicate that targeted inhibition of hedgehog signaling by Smo signaling inhibitor KAAD-cyclopamine causes hedgehog target gene expression (Gli1) suppression, induces P21 expression and G1 cell population, and reduced expression of Cyclin D1 and IGF2.
These results indicate that hedgehog signaling activation is a very common event in pancreatic cancer and that targeted inhibition of hedgehog signaling may be effective in treatment of pancreatic cancer.
胰腺癌是一种侵袭性恶性肿瘤，预后不良。胰腺癌的总 5 年生存率低于 5%，多年来并未显著改善。进一步了解胰腺癌的分子致癌机制对于设计治疗这种恶性肿瘤的有效方法至关重要。
在这项研究中，我们检查了 54 个手术切除的胰腺癌标本和 7 个可用的胰腺癌细胞系中 hedgehog 信号分子的表达。
我们发现 Ptch 的表达与肿瘤大小、肿瘤分化、淋巴结转移和临床分期有关，而 Smo 的表达与肿瘤分化和淋巴结转移有关。我们对胰腺癌细胞系的研究表明，Smo 信号抑制剂 KAAD-cyclopamine 靶向抑制 hedgehog 信号会导致 hedgehog 靶基因表达（Gli1）抑制，诱导 P21 表达和 G1 细胞群，并降低 Cyclin D1 和 IGF2 的表达。
这些结果表明 hedgehog 信号激活是胰腺癌中非常常见的事件，靶向抑制 hedgehog 信号可能对治疗胰腺癌有效。
