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[Anticancer effects of tea polyphenols on colorectal cancer with microsatellite instability in nude mice]
Gong-jian Dai1, Hei-ying Jin, Yi-jiang Ding
1Department of Gastroenterology Surgery, the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210082, China.
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.
Insights
Tea polyphenols demonstrate anticancer effects against microsatellite instability (MSI) colorectal cancer in mice. This study shows tea polyphenols can inhibit tumor growth by down-regulating MSI.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Context:
- Colorectal cancer (CRC) with microsatellite instability (MSI) presents unique therapeutic challenges.
- Understanding the molecular mechanisms underlying MSI CRC is crucial for developing targeted treatments.
- Nude mouse models offer a platform for evaluating novel anticancer agents.
Purpose:
- To investigate the efficacy of tea polyphenols as an anticancer agent against MSI colorectal cancer.
- To elucidate the mechanism by which tea polyphenols affect MSI and tumor growth in a preclinical model.
- To assess the impact of tea polyphenols on key molecular markers including MSI and growth factors.
Summary:
- Tea polyphenols were administered to nude mice bearing MSI colorectal tumors.
- Significant tumor growth inhibition was observed in tea polyphenol-treated groups compared to controls.
- Treatment with tea polyphenols led to a stabilization of microsatellite instability (MSI) markers.
Impact:
- Tea polyphenols show potential as a therapeutic agent for MSI colorectal cancer.
- Down-regulation of MSI by tea polyphenols offers a novel therapeutic strategy.
- This research provides a basis for further investigation into tea polyphenols for cancer treatment.
