Curcumin Synergistically Increases Effects ofβ-Interferon and Retinoic Acid on Breast Cancer Cells In Vitro and In Vivo by Upregulation of GRIM-19 through STAT3-dependent and STAT3-independent Pathways.
J Drug Target. 2016 Sep 28:1-23. Epub 2016 Sep 28. PMID: 27677346
OBJECTIVE: The study aimed to investigate the effects of combination treatment of curcumin and IFN-β/RA on breast cancer cells, including cell viability, apoptosis and migration, and to determine the mechanisms related to GRIM-19 through STAT3-dependent and STAT3-independent pathways.
METHODS: The following groups were used for the in vitro experiment: control siRNA, GRIM-19 siRNA, IFN-β/RA and IFN-β/RA+curcumin. Cell viability is by the MTT method, cell apoptosis by flow cytometry and cell migration by wound healing experiment; GRIM-19, STAT3, Survivin, Bcl-2, GADD153 and COX-2 expression was measured by western blot. In vivo experiment, MCF-7 cells were subcutaneously injectedinto nude mice.
RESULTS: GRIM-19 siRNA promoted MCF-7 cell proliferation and migration; inhibited cell apoptosis; and promoted the expression of STAT3, Survivin, Bcl-2 and MMP-9. IFN-β/RA inhibited cell proliferation and migration; promoted cell apoptosis; upregulated GRIM-19; and inhibited the expression of STAT3, Survivin, Bcl-2 and MMP-9. Combination treatment of curcumin and IFN-β/RA had a stronger effect than that of the IFN-β/RA group. In addition, curcumin and IFN-β/RA combination inhibited the expression of COX-2 and upregulated GADD153.
CONCLUSION: Curcumin synergistically increases the effects of IFN-β/RA on breast cancer cells. The mechanism may be related to the upregulation of GRIM-19 through STAT3-dependent and STAT3-independent pathways.