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Journal of Chinese Integrative Medicine ›› 2008, Vol. 6 ›› Issue (12): 1263-1266.doi: 10.3736/jcim20081211

• Original Experimental Research • Previous Articles     Next Articles

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

Gong-jian Dai1, Hei-ying Jin2(), Yi-jiang Ding2, Jian-guo Xia1, Xiu-fang Liu2, Fei Liu2, Xuan-zhong Tan2, Jian-xiang Geng2   

  1. 1. Department of Gastroenterology Surgery, the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210082, China
    2. National Medical Center of Anorectal Surgery, the Third Affiliated Hospital, Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu Province 210001, China
  • Received:2008-07-11 Online:2008-12-20 Published:2008-12-15

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-β1 (TGF-β1), TGF-β2 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-β1, TGF-β2, 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.

Key words: tea polyphenols, DNA mismatch repair, gene deletion, colorectal neoplasms, microsatellite instability, nude mice

CLC Number: 

  • R735.35

Figure 1

Tumor inhibition rates after tea polyphenols injection in different groups **P<0.01, vs tea polyphenols-treated groups, n=10."

Table 1

Changes of MSI signs and TGFβ1, TGFβ2 and IGF in untreated group"

Gene Before treatment 3 days 1 weeks 2 weeks 3 weeks 4 weeks
BAT-25 peak 1 117.0 116.9 118.1 117.8 119.2 119.3
BAT-25 peak 2 120.1 120.2 120.2 119.0
BAT-26 peak 1
BAT-26 peak 2
D2S123 peak 1 206.9 209.0 207.3 206.9 209.1 211.1
D2S123 peak 2 214.9 216.4 215.2 214.8 217.0 212.3
D5S346 peak 1 110.1 108.2 107.9 107.4 108.0 108.0
D17S250 peak 1 144.5 144.5 145.9 144.5 144.9 145.1
D17S250 peak 2 155.7 152.0 158.0 159.3 157.9 158.1
TGFβ1 peak 1 85.2 83.9 84.0 84.1 84.1 84.1
TGFβ2 peak 1 125.2 126.2 126.1 125.0 125.0 125.1
IGF peak 1 108.0 107.7 107.9 108.1 108.1 108.1

Table 2

Changes of MSI signs and TGF-β1, TGF-β2 and IGF after 75 mg/kg tea polyphenols treatment"

Gene Before treatment 3 days 1 weeks 2 weeks 3 weeks 4 weeks
BAT-25 peak 1 117.0 116.9 118.1 117.8 118.2 118.3
BAT-25 peak 2 120.1 120.2
BAT-26 peak 1
BAT-26 peak 2
D2S123 peak 1 206.9 208.8 207.3 206.9 207.2 207.4
D2S123 peak 2 214.9 214.7 215.2 214.8 217.0 215.2
D5S346 peak 1 110.1 108.2 107.9 107.4 108.0 108.0
D17S250 peak 1 144.5 144.5 145.9 144.5 144.9 145.1
D17S250 peak 2 155.7 152.0 158.0 159.3 157.9 158.1
TGF-β1 peak 1 85.2 83.9 84.0 84.1 84.1 84.1
TGF-β2 peak 1 125.2 126.2 126.1 125.0 125.0 125.1
IGF peak 1 108.0 107.7 107.9 108.1 108.1 108.1
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