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Curcumin Inhibits Proliferation of Renal Cell Carcinoma in vitro and in vivo by Regulating miR-148/ADAMTS18 through Suppressing Autophagy

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Abstract

Objective

To explore the effect of curcumin on the proliferation of renal cell carcinoma and analyze its regulation mechanism.

Methods

In RCC cell lines of A498 and 786-O, the effects of curcumin (2.5, 5, 10 µ mo/L) on the proliferation were analyzed by Annexin V+PI staining. Besides, A498 was inoculated into nude mice to establish tumorigenic models, and the model mice were treated with different concentrations of curcumin (100, 200, and 400 mg/kg), once daily for 30 days. Then the tumor diameter was measured, the tumor cells were observed by hematoxylin-eosin staining, and the protein expressions of miR-148 and ADAMTS18 were detected by immunohistochemistry. In vitro, after transfection of miR-148 mimics, miR-148 inhibitor or si-ADAMTS18 in cell lines, the expression of ADAMTS18 was examined by Western blotting and the cell survival rate was analyzed using MTT. Subsequently, Western blot analysis was again used to examine the autophagy phenomenon by measuring the relative expression level of LC3-II/LC3-I; autophagy-associated genes, including those of Beclin-1 and ATG5, were also examined when miR-148 was silenced in both cell lines with curcumin treatment.

Results

Curcumin could inhibit the proliferation of RCC in cell lines and nude mice. The expression of miR-148 and ADAMTS18 was upregulated after curcumin treatment both in vitro and in vivo (P<0.05). The cell survival rate was dramatically declined upon miR-148 or ADAMTS18 upregulated. However, si-ADAMTS18 treatment or miR-148 inhibitor reversed these results, that is, both of them promoted the cell survival rate.

Conclusion

Curcumin can inhibit the proliferation of renal cell carcinoma by regulating the miR-148/ ADAMTS18 axis through the suppression of autophagy in vitro and in vivo. There may exist a positive feedback loop between miR-148 and ADAMTS18 gene in RCC.

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Authors and Affiliations

  1. Depatment of Urology, Peking University First Hospital, Beijing, 100034, China

    Ben Xu, Chang-wei Yuan & Jia-en Zhang

Authors
  1. Ben Xu
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  2. Chang-wei Yuan
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  3. Jia-en Zhang
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Contributions

Xu B carried out the design of this research, analysis and interpretation of data, and drafted the manuscript. Yuan CW participated in the collection of data and data analysis. Zhang JE 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.

Supported by Beijing Traditional Chinese Medicine Development Fundation (No. QN-2020-03)

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Xu, B., Yuan, Cw. & Zhang, Je. Curcumin Inhibits Proliferation of Renal Cell Carcinoma in vitro and in vivo by Regulating miR-148/ADAMTS18 through Suppressing Autophagy. Chin. J. Integr. Med. 29, 699–706 (2023). https://doi.org/10.1007/s11655-022-3690-9

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  • DOI: https://doi.org/10.1007/s11655-022-3690-9

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