Curcumin Inhibits Hepatocellular Carcinoma via Regulating miR‐21/TIMP3 Axis

Background/Aim . Curcumin exhibits anticancer effects against various types of cancer including hepatocellular carcinoma (HCC). miR‐21 has been reported to be involved in the malignant biological properties of HCC. However, whether miR‐21 plays a role in curcumin‐mediated treatment of HCC is unknown. The purpose of this study was to identify the potential functions and mechanisms of miR‐21 in curcumin‐mediated treatment of HCC. Methods . The anticancer effects of curcumin were assessed in vivo and in vitro. The underlying mechanism of miR‐21 in curcumin‐mediated treatment of HCC was assessed by quantitative real‐time PCR (RT‐qPCR), western blot, and Dual‐Luciferase Reporter assays. Results . The present study revealed that curcumin suppressed HCC growth in vivo and inhibited HCC cell proliferation and induced cell apoptosis in a dose‐dependent manner in vitro. Meanwhile, the curcumin treatment can downregulate miR‐21 expression, upregulate TIMP3 expression, and inhibit the TGF‐ β 1/smad3 signaling pathway. miR‐21 inhibition enhanced the effect of curcumin on cell proliferation inhibition, apoptosis, and TGF‐ β 1/smad3 signaling pathway inhibition in HepG2 and HCCLM3 cells. It demonstrated that TIMP3 was a direct target gene of miR‐21. Interestingly, the effect of miR‐21 inhibition on cell proliferation, apoptosis, and TGF‐ β 1/smad3 signaling pathway in HepG2 and HCCLM3 cells exposed to curcumin was attenuated by TIMP3 silencing. Conclusion . Taken together, the present study suggests that miR‐21 is involved in the anticancer activities of curcumin through targeting TIMP3, and the mechanism possibly refers to the inhibition of TGF‐ β 1/smad3 signaling pathway.