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Curcumin Inhibits Viability of Clear Cell Renal Cell Carcinoma by Down-Regulating ADAMTS18 Gene Methylation though NF-κ B and AKT Signaling Pathway

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Abstract

Objective

To investigate the effect of curcumin on viability of clear cell renal cell carcinoma (ccRCC) and analyze its possible mechanism.

Methods

In cell lines of A498 and 786-O, the effects of curcumin (1.25, 2.5, 5 and 10 μ mol/L) on the viability of ccRCC 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 (pAKT) and matrix metallopeptidase 2 (MMP-2) before and after curcumin (10 μ mol/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 (10 μ mol/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 factor κ B (NF-κ kB) related protein (p65 and pp65), AKT related protein (AKT and pAKT), and NF-κ B/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, pAKT and MMP2 in sh-ADAMTS18 was down-regulated after being treated with PDTC (NF-κ B inhibitor) and LY294002 (AKT inhibitor).

Conclusions

Curcumin could inhibit the viability of ccRCC by down-regulating ADAMTS18 gene methylation though NF-κ B and AKT signaling pathway.

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Authors and Affiliations

  1. Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, National Urological Cancer Center, Beijing, 100034, China

    Ben Xu, Yi-ji Peng & Wei-jie Zhu

Authors
  1. Ben Xu
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  2. Yi-ji Peng
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  3. Wei-jie Zhu
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Contributions

Xu B carried out the design of this research, analysis and interpretation of data, and drafted the manuscript. Peng YJ participated in the collection of data and data analysis. Zhu WJ assisted in the design of this research and project development. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ben Xu.

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There is no conflict of interest involved in this manuscript.

Additional information

Supported by the Beijing Natural Science Foundation (No. 7204316), Beijing Traditional Chinese Medicine Development Fundation (No. QN-2020-03) and Peking University Medicine Fund of Fostering Young Scholars’ Scientific & Technological Innovation (No. BMU2020PYB018)

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Xu, B., Peng, Yj. & Zhu, Wj. Curcumin Inhibits Viability of Clear Cell Renal Cell Carcinoma by Down-Regulating ADAMTS18 Gene Methylation though NF-κ B and AKT Signaling Pathway. Chin. J. Integr. Med. 28, 419–424 (2022). https://doi.org/10.1007/s11655-021-3445-z

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  • DOI: https://doi.org/10.1007/s11655-021-3445-z

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