Curcumin synergistically increases effects of β-interferon and retinoic acid on breast cancer cells in vitro and in vivo by up-regulation of GRIM-19 through STAT3-dependent and STAT3-independent pathways.
The study aimed to investigate the effects of combination treatment of curcumin and β-interferon (IFN-β)/retinoic acid (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.



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 injected into nude mice.



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; up-regulated 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 up-regulated GADD153.



Curcumin synergistically increases the effects of IFN-β/RA on breast cancer cells. The mechanism may be related to the up-regulation of GRIM-19 through STAT3-dependent and STAT3-independent pathways.
a Department of Breast Surgery , The First Affiliated Hospital of Anhui Medical University , Hefei , P.R. China.
Min
M
Ren
b Central Sterile Supply Department , Anhui Provincial Hospital of Anhui Medical University , Hefei , P.R. China.
Ying
Y
Wang
a Department of Breast Surgery , The First Affiliated Hospital of Anhui Medical University , Hefei , P.R. China.
Xiaodong
X
Wu
a Department of Breast Surgery , The First Affiliated Hospital of Anhui Medical University , Hefei , P.R. China.
Suxia
S
Ge
a Department of Breast Surgery , The First Affiliated Hospital of Anhui Medical University , Hefei , P.R. China.
Benzhong
B
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D003474:Curcumin / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
D051017:Apoptosis Regulatory Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014212:Tretinoin; D016899:Interferon-beta; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human; D003474:Curcumin
Curcumin; GRIM-19; STAT3; all-trans retinoic acid; β-interferon