Establishment and characterization of human gastric and colonic xenograft lines resistant to CPT-11 (A new derivative of camptothecin)

✍ Scribed by Satoshi Nagai; Masaji Yamauchi; Toshiwo Andoh; Miwako Nishizawa; Tetsuya Satta; Yasuhiro Kodera; Ken Kondou; Seiji Akiyama; Katsuki Ito; Hiroshi Takagi

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 813 KB
• Volume: 59
• Category: Article
• ISSN: 0022-4790
• DOI: 10.1002/jso.2930590209

✦ Synopsis

CPT-1 1 -resistant human gastric and colonic xenograft lines were established by direct intratumoral injection of CPT-11 into subcutaneous SC-1-NU and CC-2-NU tumors in nude mice once a week for 10 months. The resistance of these xenograft lines to CPT-11 was confirmed by growth inhibition rate, to be 36.3% and 45.4%, respectively, compared to each parent cell line. DNA topoisomerase I activity of the nuclear extracts of SC-1 -NU/CPT-1 1 and CC-2-NUKFT-1 1, as assayed by relaxation of supercoiled DNA Col-El, was significantly less than those of the parent lines. The cellular levels of topoisomerase I in those resistant lines measured by Western blot analysis were 0.57-and 0.79-fold lower than those of the parental lines, respectively. However, the activity of DNA topoisomerase I1 of those resistant cell lines assayed by decatenation of kinetoplast DNA was higher than that of the parental lines and the cellular levels of topoisomerase I1 in the resistant lines measured by Western blot analysis were 10.8-and 8. l-fold higher than those of the parent lines. Intracellular accumulation of CPT-11 in CPT-1 l-resistant tumors was not changed as compared to that of the parental lines, but hydrolysis of CPT-11 to more active SN-38 was reduced in the resistant tumors.