The antitumor activity of meisoindigo against human colorectal cancer HT-29 cells in vitro and in vivo.
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.
Mingxin
Zuo
Z
Institute of Meteria Medica, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, PR China.
Yan
Li
L
Hongbo
Wang
W
Jianhua
Zhou
Z
Hongyan
Li
L
He
Liu
L
Hongqi
Xin
X
Sen
Zhang
Z
Xiaoguang
Chen
C
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
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