Effects of rhein derivatives 4 a containing amide structure on migration and invasion in ovarian cancer cells / 中国药理学通报

ABSTRACT

Aim To investigate the effect of Rhein derivative 4a containing amide structure on migration and invasion in ovarian cancer SKOV3 cells and its possible mechanism. Methods Ovarian cancer SK0V3 cells were used as target cells. Molecular docking and West-em blot were used to detect the regulatory effect of derivative 4a on Racl protein. CCK8, HE staining, Scratch and Transwell assay were used to detect the effects of derivative 4a on the proliferation, morphology , migration and invasion of SK0V3 cells, respectively. Western blot was employed to determine the expression of matrix metalloproteinases and EMT-related proteins. Results Derivative 4a could effectively bind to Racl protein, and the binding energy was-29. 10 kcal • mol"1, which was significantly lower than that of Rhein; it also could down-regulate the expression of Racl protein in SK0V3 cells. Derivative 4a could significantly inhibit the proliferation, invasion and migra tion of SKOV3 cells, and induce a large amount of cellular vacuolation; derivative 4a could also down-regu-\ late the expression of MMP-2 and MMP-9, up-regulate the expression of EMT epithelial marker protein E-ca-derin but down-regulate the expression of vimentin and j3-cantenin. Conclusions Derivative 4 a can inhibit the proliferation, migration and invasion of ovarian cancer SK0V3 cells. The mechanism may relate to its targeted regulation of Racl, thereby inhibiting the secretion of matrix metalloproteinases, up-regulating the expression of key molecule E-caderin and down-regula-ting the expression of Vimentin and (3-cantenin in EMT i process.•.