CPT-11 may provide therapeutic efficacy for esophageal squamous cell cancer and the effects correlate with the level of DNA topoisomerase I protein.

Abstract

CPT-11 is a potent anti-cancer drug and a specific inhibitor of DNA topoisomerase I (Topo I). In this study, we aim to evaluate the effects of CPT-11 on esophageal squamous cell cancers (ESCC) and to determine the correlation between the effects and the levels of Topo I expression. We examined the growth-inhibitory effect caused by SN-38, an active metabolite of CPT-11, in 14 human ESCC cell lines established from 10 primary and 4 metastatic lesions. CPT-11 was considered effective against 5 cell lines from primary lesions and one from metastatic lesions, and thus may show therapeutic efficacy against both primary and metastatic ESCC tumors. Although Topo I mRNA levels in these 14 ESCC cell lines, as quantitated by northern blot analysis, showed no correlation with the IC(50) values, Topo I protein levels, as quantitated by western blot analysis, showed an inverse correlation with the IC(50) values. Topo I protein levels could be an indicator of sensitivity to CPT-11. We also determined Topo I protein levels in 40 ESCC tumors and matched normal mucosae. Thirty-four tumors showed 1.2 - 22.3-fold increases in Topo I levels. Two patients receiving pre-operative chemotherapy and one receiving radiotherapy exhibited increased Topo I protein levels in their tumor lesions. It appeared that CPT-11 could provide selective therapeutic efficacy against ESCC tumors. CPT-11 may be effective for the treatment of metastatic ESCC tumors and as a second-line anti-cancer drug for ESCC.

• Authors: Y Nakajima, S Miyake, K Nagai, T Kawano, T Iwai
• Journal: Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 92 Issue 12 Pg. 1335-41 (Dec 2001) ISSN: 0910-5050 [Print] Japan
• PMID: 11749700 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Irinotecan
• DNA Topoisomerases, Type I
• Camptothecin

Topics

• Blotting, Western
• Camptothecin (analogs & derivatives, pharmacology, therapeutic use)
• Cell Division (drug effects)
• DNA Topoisomerases, Type I (metabolism)
• Dose-Response Relationship, Drug
• Esophageal Neoplasms (drug therapy, enzymology)
• Humans
• Irinotecan
• Neoplasms, Squamous Cell (drug therapy, enzymology)
• RNA, Messenger (metabolism)
• Tumor Cells, Cultured