胰腺癌SMO靶标治疗研究启示:从中药中发现新药(英文)  

Advances in Smoothened-targeting therapies for pancreatic cancer:implication for drug discovery from herbal medicines

作　　者：韩尽斌[1] 花永强[1] 陈联誉[1] 刘鲁明[1] 

机构地区：[1]复旦大学肿瘤医院中西医结合科,上海200032

出　　处：《中西医结合学报》2012年第3期256-263,共8页Journal of Chinese Integrative Medicine

基　　金：国家自然科学基金面上项目资助项目(No.81072942);国家自然科学基金青年科学基金资助项目(No.30901911)

摘　　要：跨膜蛋白Smoothened(SMO)是音猬因子(sonic hedgehog homology,SHH)信号转导通路的主要成员,在SHH通信过程里发挥桥梁作用。在多种肿瘤组织中均可以检测到SHH的异常表达,胰腺癌干细胞SHH信号的表达明显高于普通胰腺癌细胞。SHH信号与肿瘤干细胞的自我复制,肿瘤血管和基质形成密切相关。使用以环巴胺、GDC-0449等SMO拮抗剂可以抑制SHH信号的异常转导,有效阻止肿瘤的生长和转移。目前已有多种SMO拮抗剂作为抗肿瘤药物进入Ⅰ期或Ⅱ期临床试验,已经有以SMO拮抗剂治疗胰腺癌的Ⅰ期临床试验。作为经典的SMO拮抗剂,环巴胺是从传统药用植物中提取出来的生物碱,这可能为中医药研究者提供思路,从中药中研发更加有效的SMO拮抗剂。Smoothened （SMO） is a member of sonic hedgehog homology （SHH） signaling pathway. It plays a key role as a bridge between patched-1 （PTCH-1） and Gli. Aberrant SHH expression can be detected in various malignant tissues, and the expression in pancreatic cancer stem cells is higher apparently. SHH signals are closely associated with self-duplication of cancer stem cells, formation of tumor vessels as well as matrixes. SMO antagonists such as cyclopamine, GDC-0449 and so on show potential to inhibit activity of SHH signaling, and arrest the growth as well as metastases of tumors. Recently, a few of SMO antagonists have been studied in phase Ⅰ clinical trials and some are in phase Ⅱ, meanwhile, phase Ⅰ or Ⅱ trials of SMO antagonists to treat pancreatic cancer are performed currently. As the classical SMO antagonist, cyclopamine is extracted from a medicinal plant. Perhaps researchers may be able to determine more effective SMO-targeting drugs from herbal medicines in the future.

关 键 词：胰腺肿瘤 肿瘤干细胞 SMOOTHENED 猬蛋白质类 信号传导 植物 药用 综述 

分 类 号：R735.9[医药卫生—肿瘤]