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

作     者：XU Ben YUAN Chang-wei ZHANG Jia-en 

作者机构：Depatment of UrologyPeking University First HospitalBeijing(100034)China 

出 版 物：《Chinese Journal of Integrative Medicine》 (中国结合医学杂志（英文版）)

年 卷 期：2023年第29卷第8期

页      面：699-706页

核心收录：

学科分类：1006[医学-中西医结合] 1002[医学-临床医学] 10[医学] 100602[医学-中西医结合临床] 

基　　金：Beijing Traditional Chinese Medicine Development Fundation(No.QN-2020-03)。 

主　　题：curcumin renal cell carcinoma MiR-148 ADAMTS18 gene autophagy 

摘      要：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 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 ADAMTS18were 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 expressions of miR-148 and ADAMTS18 were upregulated after curcumin treatment both in vitro and in vivo(P0.05). 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 mi R-148 and ADAMTS18 gene in RCC.