Impacts of muscone on malignant progression of ovarian cancer cells by regulating SHH mediated autophagy
Objective To investigate the effect of muscone on malignant progression of ovarian cancer cells mediated by regulating sonic hedgehog(SHH)mediated autophagy.Methods Survival rates of human ovarian cancer cell line SKOV3 treated with 0,2,4,8,16,and 24 μmol/L muscone were detected,and the optimal cell action concentration of muscone was selected.SKOV3 cells were cultured in vitro,and their transplanted tumor mouse models were constructed.Cells were randomly grouped into the control group,the muskone group,the muskone+chloroquine(CQ,an autophagy inhibitor)group,the muskone+empty group and the muskone+SHH overexpression group.After grouping and treatment with musconeand,CQ,empty plasmid and SHH overexpression plasmid,the tumor volume and weight in transplanted tumor mice were detected.EdU staining,TUNEL staining,cell scratch,Transwell invasion assay,immunoblotting and real-time fluorescence quantitative PCR were used to detect proliferation,apoptosis,migration and invasion of SKOV3 cells,the expression of autophagy related proteins(LC3Ⅱ/LC3Ⅰ,Beclin-1)and SHH in SKOV3 cells and transplanted tumor mice in each.Results Compared with the control group,the cell proliferation rate,cell migration rate,number of invasions,tumor volume and weight,and the expression of SHH mRNA and protein in tumor tissue were decreased in the muskone group(P<0.05),and the apoptosis rate,LC3Ⅱ/LC3Ⅰ,Beclin-1 protein in cells and tumor tissue were increased(P<0.05).Compared with the muscone group,the cell proliferation rate,cell migration rate,number of invasion,tumor volume and weight were increased in the muscone+CQ group and the muskone+SHH overexpression group(P<0.05),and the apoptosis rate,LC3Ⅱ/LC3Ⅰ and the expression of Beclin-1 protein in cells and tumor tissue were decreased(P<0.05).There were no significant differences in the above indicators in the muscone+empty group(P>0.05).Conclusion Muscone can promote autophagy of ovarian cancer cells by down-regulating SHH,thereby inhibiting their proliferation,in vivo growth,migration and invasion,promoting their apoptosis,and ultimately inhibiting their malignant progression.
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