Objective:

2

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

Methods:

2

In RCC cell lines of A498 and 786-O

the effects of curcumin (2.5

5

10 μmo/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:

2

Curcumin could inhibit the proliferation of RCC in cell lines and nude mice. The expressions of miR-148 and ADAMTS18 were 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:

2

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.