CPT‐11 May Provide Therapeutic Efficacy for Esophageal Squamous Cell Cancer and the Effects Correlate with the Level of DNA Topoisomerase I Protein

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.