title: The antitumor activity of meisoindigo against human colorectal cancer HT-29 cells in vitro and in vivo.
abstract: 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 (IC(50) 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-3beta(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-3beta, GSK-3beta(ser(9)) phosphorylation in Wnt signaling pathway. These findings indicate the potential value of meisoindigo for the treatment of colorectal cancer.
authors.affiliation: Institute of Meteria Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, PR China.
authors.forename: Zuo
authors.initials: Z
authors.lastname: Mingxin
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.forename: Wang
authors.initials: W
authors.lastname: Hongbo
authors.forename: Zhou
authors.initials: Z
authors.lastname: Jianhua
authors.forename: Li
authors.initials: L
authors.lastname: Hongyan
authors.forename: Liu
authors.initials: L
authors.lastname: He
authors.forename: Xin
authors.initials: X
authors.lastname: Hongqi
authors.forename: Zhang
authors.initials: Z
authors.lastname: Sen
authors.forename: Chen
authors.initials: C
authors.lastname: Xiaoguang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects*; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects; D000071679:Glycogen Synthase Kinase 3 beta; D019073:HT29 Cells; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D051153:Wnt Proteins; C047330:N-methylisoindigotin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3