Exploring The Anti-tumor Effect Of Lycorine Targeting NF-κB Signaling Pathway

NF-κB signaling pathway is one of more thorough research to the signaling known, involved in almost all of the tumorigenesis processes, including cell proliferation, apoptosis, angiogenesis and so on. At present the NF-κB signaling pathway has become hot spots for the malignant tumor of the drugs treatment. Lycorine, a natural alkaloid derived from the plant Amarylidaceae, have been report to exhibit various biological effects on tumor cells. However the mechanism of action remains unclear.Here, our study was foused on anti-tumorigenic effects and detailed mechanism of lycorine on prostate cancer based on NF-κB signaling pathway which plays a critical role in tumorigenesis.Our studies showed that lycorine inhibited NF-κB activation and its regulated reporter gene expression. Western blot assay indicated that lycorine inhibited the expression of phosphorylation IkB-α(p-IkBα), IkB-α degradation, and phosphorylation p65. And the nuclear translocate of p65 cloud blocked by lycorine. Besides the overexpressed assay might indicated that lycorine might inhibited NF-κB activation via directly target IKKβ. Then we evaluated its antitumor activity found that lycorine arrest cycle in G2/M phase, inhibited cell cycle related genes p21 and cyclinD1 expression. And lycorine induced apoptosis in PC3 and DU145 cells, and induced PARP cleaving. Furthermore, the C57/BL-RM-1 mouse model were built to evaluate the anti-tumor effect of lycorine in vivo. Tumor weight showed that lycorine significantly inhibit tumor growth.H&E staining showed that lycorine promote tumor issue damage. Immunohistochemistry and immunofluorescence assay was performed to inhibite the expression of p65, IKKβ, KI-67,survivin and Caspase 3 in vivo, which confirm the inactivation of NF-κB signaling pathway.Above all, lycorine can inhibit the growth of prostate cancer cells by reduced the NF-κB signaling pathway activity. Our study in part advanced our understanding of the mechanism by which lycorine modulates the anti-tumor activity.