title: 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.affiliation: Department of Neurosurgery, Clinical Neuroscience Center, Seoul National University Bundang Hospital, Seoul, South Korea.
authors.forename: Chae-Yong
authors.initials: CY
authors.lastname: Kim
authors.forename: Su-Jung
authors.initials: SJ
authors.lastname: Lee
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Kim
authors.forename: Chul-Kee
authors.initials: CK
authors.lastname: Park
authors.forename: Kyu-Chang
authors.initials: KC
authors.lastname: Wang
authors.forename: Byung-Kyu
authors.initials: BK
authors.lastname: Cho
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D059004:Topoisomerase I Inhibitors / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; C116963:belotecan; D002166:Camptothecin