摘要
Objective:To investigate the effect of curcumin on viability of clear cell renal cell carcinoma(cc RCC)and analyze its possible mechanism.Methods:In cell lines of A498 and 786-O,the effects of curcumin(1.25,2.5,5 and 10μmol/L)on the viability of cc RCC were analyzed at 24,48 and 72 h by MTT assay.The protein expression levels of ADAMTS18 gene,p65,phosphorylation p65(pp65),AKT,phosphorylation AKT(p AKT)and matrix metallopeptidase 2(MMP-2)before and after curcumin(10μmol/L)treatment were examined by Western blotting.Real-time PCR and methylation specific PCR(MSP)were applied to analyze the expression and methylation level of ADAMTS18 gene before and after curcumin treatment(10μmol/L).Results:Curcumin significantly inhibited the viability of A498 and 786-O cell lines in a dose-and time-dependent manner(P<0.01).Up-regulation of ADAMTS18 gene expression with down-regulation of ADAMTS18 gene methylation was reflected after curcumin treatment,accompanied by down-regulation of nuclear factorκB(NF-κk B)related protein(p65 and pp65),AKT related protein(AKT and p AKT),and NF-κB/AKT common related protein MMP-2.With ADAMTS18 gene overexpressed,the expression levels of p65,AKT and MMP2 were downregulated,of which were conversely up-regulated in silenced ADAMTS18(sh-ADAMTS18).The expression of pp65,p AKT and MMP2 in sh-ADAMTS18 was down-regulated after being treated with PDTC(NF-κB inhibitor)and LY294002(AKT inhibitor).Conclusion:Curcumin could inhibit the viability of cc RCC by down-regulating ADAMTS18 gene methylation though NF-κB and AKT signaling pathway.
基金
Supported by the Beijing Natural Science Foundation(No.7204316)
Beijing Traditional Chinese Medicine Development Fundation(No.QN-2020-03)
Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological Innovation(No.BMU2020PYB018)。
