Journal
CANCER CHEMOTHERAPY AND PHARMACOLOGY
Volume 79, Issue 5, Pages 985-994Publisher
SPRINGER
DOI: 10.1007/s00280-017-3301-1
Keywords
Prostate cancer; Curcumin; FOXD3/miR143; PGK1
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Funding
- Project for Key Disease Type of Chinese and Western Integrative Medicine, Shanghai Municipal Commission of Heath and Family Planning: Special Subject Construction of Treating Prostatic Cancer by Chinese and Western Integrative Medicine [ZXBZ2012-07]
- Project of Establishing Working Studio of Shanghai Doctor of Traditional Chinese Medicine, Zhou Zhiheng [ZYSNXD-CC-MZY011]
- three year plan of Shanghai to further accelerate the development of traditional Chinese Medicine [ZY3-RCPY-3-1012]
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Curcumin is a potent antitumor agent. The objective of this study was to explore the interaction between curcumin and PGK1, an oncogene in the FOXD3/miR-143 axis, in prostate cancer therapy. MiRNA microarray analysis was used to identify miRNAs upregulated by curcumin treatment. MiR-143 was dramatically upregulated by curcumin. Cells were treated with antimiR-143 in combination to curcumin, followed by examining cell viability and migration. Bioinformatics analysis was used to investigate target genes of miR-143. The interaction between miR-143 and PGK1 was evaluated with dual-luciferase assay. Since FOXD3 is important in the regulation of miR-143, we explored whether curcumin regulated FOXD3 expression. FOXD3 was also ectopically overexpressed to investigate its effects on curcumin's regulation of miR-143. Curcumin treatment significantly upregulated miR-143 and decreased prostate cancer cell proliferation and migration. Those effects were attenuated by anti-miR-143 transfection. Both miR-143 overexpression and curcumin treatment inhibited PGK1 expression and ectopic expression of PGK1 antagonized curcumin's antitumor effects. FOXD3 was upregulated by miR-143. Ectopic expression of FOXD3 synergized with curcumin in upregulating miR-143 expression. Curcumin inhibits prostate cancer by upregulating miR-143. PGK1 is downregulated by miR-143, and FOXD3 upregulation is essential for the antitumor effect of curcumin.
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