CAJ | 학술논문

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.
과막단백Smoothened(SMO)시음위인자(sonic hedgehog homology,SHH)신호전도통로적주요성원,재SHH통신과정리발휘교량작용.재다충종류조직중균가이검측도SHH적이상표체,이선암간세포SHH신호적표체명현고우보통이선암세포.SHH신호여종류간세포적자아복제,종류혈관화기질형성밀절상관.사용이배파알、GDC-0449등SMO길항제가이억제SHH신호적이상전도,유효조지종류적생장화전이.목전이유다충SMO길항제작위항종류약물진입Ⅰ기혹Ⅱ기림상시험,이경유이SMO길항제치료이선암적Ⅰ기림상시험.작위경전적SMO길항제,배파알시종전통약용식물중제취출래적생물감,저가능위중의약연구자제공사로,종중약중연발경가유효적SMO길항제.
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.