[Tea polyphenol inhibits colorectal cancer with microsatellite instability by regulating the expressions of HES1, JAG1, MT2A and MAFA].
OBJECTIVE
To investigate the mechanism of tea polyphenol in inhibiting microsatellite instability (MSI) of colorectal cancer.


METHODS
Using LoVo cells and SW480 cells treated with aqueous solution of tea polyphenol, cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) method, changes in microsatellite sequences were detected by genescan method and changes in gene expression of LoVo cells were detected by illumina expression arrays and quantitative real-time polymerase chain reaction (PCR).


RESULTS
The proliferation inhibition rates of LoVo and SW480 cells treated with tea polyphenol increased with the increasing of drug concentration and showed an increasing tendency with time. The proliferation inhibition rate of LoVo cells with tea polyphenol was higher than that of SW480 cells, and there was a significant difference in the proliferation inhibition rates at 24 h, 72 h and one week. The microsatellite sequence of LoVo cells treated with tea polyphenol remained stable. The gene expression arrays and quantitative real-time PCR suggested that tea polyphenol inhibited the gene expressions of MT2A, MAFA, HES1 and JAG1 nearly two-fold over controls. It was also found that tea polyphenol inhibited the BAX and p38 genes with a more than two-fold difference but did not significantly inhibit the nuclear factor-κB pathway.


CONCLUSIONS
Tea polyphenol significantly inhibited the proliferation of MSI colorectal cancer cells and stably maintained the microsatellite state in MSI colorectal cancer. Tea polyphenol inhibited the gene expressions of HES1, JAG1, MT2A and MAFA, up-regulated the gene expression of BAX and down-regulated that of P38. Further research is required to investigate how these pathways are interrelated.
Xu
Yan-Yan
YY
National Center of Colorectal Surgery, The 3rd Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210001, Jiangsu Province, China.
Jin
Hei-Ying
HY
Tan
Xuan-Zhong
XZ
Liu
Xiu-Fang
XF
Ding
Yi-Jiang
YJ
D017209:Apoptosis; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D053842:Microsatellite Instability; D009363:Neoplasm Proteins / Q000378:metabolism; D059808:Polyphenols / Q000494:pharmacology*; D013662:Tea
D009363:Neoplasm Proteins; D059808:Polyphenols; D013662:Tea