| Background: Lycorine is a kind of natural alkaloid isolated from Amaryllidaceae plant,which plays an important role against various cancers with slight side effects.However,there is no report about the potential bio-activity of lycorine in colorectal cancer(CRC),detailed mechanisms of the anticancer effect of lycorine in CRC still undefined.In this study,I aim to investigate the potential function and mechanism of lycorine against CRC both in vitro and in vivo.Methods: The molecular docking modeling was used to identify potential inhibitory targets of lycorine in CRC.CCK8 assays were used to detect cell viability,apoptosis rates were measured by flow cytometry,autophagosomes in HCT116 and SW480 cell lines were tested by transmission electron microscope(TEM)and confocal microscopy.HCT116-derived xenograft model mice were constructed for examining the anti-cancer effect of lycorine.Findings: Mitogen-activated Protein Kinase Kinase2(MEK2)was predicted to be the most potential binding target of lycorine by CDOCKER prediction.According to the binding energy between the drug and proteins,MEK2 is the most potential binding protein with lowest binding energy.According to the prediction,MEK2 processed four potential interactions in conserve domains with lycorine.This prediction then was further tested by the decreased expression of phosphorylates MEK2 and its downstream(ERK and P-ERK)after lycorine treatments.Moreover,over-expression MEK2 could partially abolish lycorine induced autophagy associated apoptosis.Vemurafenib is a kind of BRAF inhibitor,this study revealed that the combination of Vemurafenib and lycorine had better effect in vitro and in vivo CRC models compared with single-drug treatment.Conclusion: This study indicates lycorine may serve as an effective MEK2 inhibitor and suggests that the combination of lycorine and Vemurafenib is a more effective therapeutic strategy for CRC than monotherapy. |
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