Wnt signaling pathway is a very conservative signaling pathway in the early development of organisms. In the normal Wnt signaling pathway, the Wnt ligand binds to the receptors Frizzled and LRP5 / 6, which can inhibit the degradation complex composed of APC and so on, so that β-catenin in the cytoplasm can be stabilized and accumulated and further enter the nucleus The combination of TCF / LEF starts the transcription of downstream genes. The abnormally activated Wnt signal is no longer regulated by the degradation complex and is closely related to the occurrence and development of various tumors, especially the mutation of the key molecule APC in Wnt signal can directly lead to colon cancer. The Wnt signaling pathway, especially the downstream β-catenin / TCF4 transcription complex, is a drug target for the treatment of colon cancer and other cancers that has emerged in recent years.
On February 15, the international academic journal Cell Research published the latest research results of the Li Lin research group of the Institute of Biochemistry and Cell, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. In this work, Wang Wei et al. Discovered a new small-molecule inhibitor 15-oxospiramilactone of the Wnt signaling pathway, and initially revealed its mechanism of action and potential for the treatment of colon cancer.
NC043 (15-oxospiramilactone) is a semi-synthetic terpenoid compound whose parent body is derived from Spiraea japonica, a traditional Chinese herbal medicine used to reduce inflammation and relieve pain. Experiments show that NC043 can effectively inhibit the expression of Wnt downstream target genes by regulating the formation of endogenous β-catenin / TCF4 transcription complex. NC043 can block colon cancer cells in the G2 / M phase, and significantly inhibits the growth of colon cancer cells than normal colon epithelial cells. The transplanted tumor experiment proves that NC043 can play a very good inhibitory effect on the transplanted tumor formed by colon cancer cells at a very low dose, and has no effect on the weight of the experimental mice. These experimental results indicate that NC043 may become a lead compound for the treatment of colon cancer. Research on the targets of direct effects and its druggability is ongoing.
This research project was completed in cooperation with the Research Group of Hao Xiaojiang, Kunming Institute of Botany, Chinese Academy of Sciences, and received financial support from the Ministry of Science and Technology, the National Natural Science Foundation of China and the Shanghai Science and Technology Commission. The achievement has applied for related patents.
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