1. Curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway.
- Author
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Tian B, Zhao Y, Liang T, Ye X, Li Z, Yan D, Fu Q, and Li Y
- Subjects
- Animals, Cell Line, Tumor, Cell Movement drug effects, Cell Proliferation, Female, Humans, Insulin-Like Growth Factor II genetics, Rats, Rats, Wistar, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Transcription, Genetic, Urinary Bladder Neoplasms metabolism, Urinary Bladder Neoplasms pathology, Curcumin pharmacology, Insulin-Like Growth Factor II antagonists & inhibitors, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, TOR Serine-Threonine Kinases metabolism, Urinary Bladder Neoplasms prevention & control
- Abstract
We have previously reported that curcumin inhibits urothelial tumor development in a rat bladder carcinogenesis model. In this study, we report that curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway. Curcumin inhibits IGF2 expression at the transcriptional level and decreases the phosphorylation levels of IGF1R and IRS-1 in bladder cancer cells and N-methyl-N-nitrosourea (MNU)-induced urothelial tumor tissue. Ectopic expression of IGF2 and IGF1R, but not IGF1, in bladder cancer cells restored this process, suggesting that IGF2 is a target of curcumin. Moreover, introduction of constitutively active AKT1 abolished the inhibitory effect of curcumin on cell proliferation, migration, and restored the phosphorylation levels of 4E-BP1 and S6K1, suggesting that curcumin functions via suppressing IGF2-mediated AKT/mTOR signaling pathway. In summary, our results reveal that suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway is one of the mechanisms of action of curcumin. Our findings suggest a new therapeutic strategy against human bladder cancer caused by aberrant activation of IGF2, which are useful for translational application of curcumin.
- Published
- 2017
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