[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. CONCLUSION: 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.

[Anticancer effects of tea polyphenols on colorectal cancer with microsatellite instability in nude mice].

OBJECTIVE: To study the anticancer effects of tea polyphenols on colorectal cancer with microsatellite instability (MSI) in nude mice and to explore its mechanism. METHODS: A colostomy was performed on the caecum of nude mice. Tumor fragments collected from the subcutaneous tumor of hMSH2-absence colon carcinoma Lovo cell line were surgically implanted onto the submucosa of the caecum during colostomy to establish the model. Then, the nude mice were divided into untreated group and 50, 75 and 100 mg/kg tea polyphenols groups. The mice in tea polyphenols-treated groups were given intra-abdominal injection of 50, 75 and 100 mg/kg tea polyphenols respectively. The inhibition rates of tumors were calculated, and microsatellite instability (MSI) and the alteration of transforming growth factor-beta1 (TGF-beta1), TGF-beta2 and insulin-like growth factor (IGF) were detected by Genescan method at different times after the injection. RESULTS: The tumor volumes of the three groups began to decrease at the 1st week and decreased most greatly from 2 to 3 weeks after treatment, and then the tumors tended to increase. The study found that tea polyphenols could inhibit the tumor growth. The tumor inhibition rates in the three treated groups were significantly higher than those in untreated group 1, 2, 3 and 4 weeks after treatment (P<0.01). Detection of MSI showed that the colorectal tumor in the untreated group presented with four MSI signs, including BAT-25, D2S123, D5S346 and D17S250, and TGF-beta1, TGF-beta2, IGF expressions. After using the tea polyphenols, the microsatellite tended to become stable. CONCLUSION: Tea polyphenols can inhibit the mismatch-repair-gene deficient colorectal cancer in nude mice by down-regulating the microsatellite instability.