Antitumor activity of CKD-602, a camptothecin derivative, in a mouse glioma model.

Abstract

CKD-602 (7-[2-(N-isopropylamino)ethyl]-(20S)-camptothecin, belotecan), a novel synthetic water-soluble camptothecin derivative, is known to have a significant anticancer effect in vitro on human glioma cell lines, including U87MG and U251MG. In the present study, we evaluated the in vivo antitumor effect of CKD-602 in a mouse glioma model. Nude mice with established U87MG glioma were treated with a dose of CKD-602 of 0mg/kg (control group, injection with saline only; n=5), 40 mg/kg (group A) or 60 mg/kg (group B). Thereafter, the dose was repeated once every 4 days for a total of four doses. Tumor volume was measured histologically and apoptosis was detected using the terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL) assay and immunofluorescence analysis with cleaved caspase-3. Mean tumor volume in each group was: control, 145.35 mm(3); group A, 76.51 mm(3); group B, 73.99 mm(3)). Tumor volume was significantly smaller in both groups A and B compared with the control group (group A, p<0.01; group B, p<0.05). Apoptosis of tumor cells was evident to a greater extent in groups A and B relative to the control group, but there were no significant differences in tumor volume or apoptotic index between groups A and B. These results suggest that CKD-602 has a significant anticancer effect on glioma cells in vivo.

• Authors: Chae-Yong Kim, Su-Jung Lee, Seung-Ki Kim, Chul-Kee Park, Kyu-Chang Wang, Byung-Kyu Cho
• Journal: Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia (J Clin Neurosci) Vol. 19 Issue 2 Pg. 301-5 (Feb 2012) ISSN: 1532-2653 [Electronic] Scotland
• PMID: 22154203 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Topoisomerase I Inhibitors
• belotecan
• Camptothecin

Topics

• Animals
• Antineoplastic Agents (therapeutic use)
• Camptothecin (analogs & derivatives, therapeutic use)
• Cell Line, Tumor
• Dose-Response Relationship, Drug
• Glioma (drug therapy, enzymology, pathology)
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Topoisomerase I Inhibitors (therapeutic use)
• Xenograft Model Antitumor Assays (methods)