Journal
JOURNAL OF CHEMOTHERAPY
Volume 20, Issue 6, Pages 728-733Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1179/joc.2008.20.6.728
Keywords
Meisoindigo; antitumor activity; Wnt signaling pathway; GSK-3 beta inhibitor; colorectal cancer
Funding
- Beijing Union Pharmaceutical Factory
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The study was conducted to examine the antitumor activity of meisoindigo on HT-29 cells in vitro and in vivo. The cytotoxicity of meisoindigo was evaluated by MTT assay. The related genes and proteins were inspected with RT-PCR and western blot assay respectively, and the effects of meisoindigo, on the cell cycle were analyzed by flow cytometry. The efficacy of meisoindigo in vivo was evaluated in an HT-29 cell xenograft nude mice model. The results show that meisoindigo effectively inhibits HT-29 cell proliferation (IC50 4.3 mmol/L), arrests HT-29 cells in G2/M phase and induces HT-29 cell apoptosis. The downstream genes and proteins of GSK-3 beta(ser(9)) expression level decrease. Meisoindigo, significantly inhibits the HT-29 xenograft tumors growth at the dose of 100 mg/kg. The mechanism of meisoindigo activity against HT-29 cells may be related to its inhibition of glycogen synthase kinase-3 beta, GSK3 beta(ser(9)) phosphorylation in Wnt signaling pathway. These findings indicate the potential value of meisoindigo for the treatment of colorectal cancer.
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