9-Nitrocamptothecin is an effective drug for the treatment of human lung tumors: comparison of in vitro and in vivo studies.
9-Nitrocamptothecin (9NC) results in complete regression of small-cell lung carcinoma (SCLC) and non-SCLC (NSCLC) growing as xenografts in immunodeficient mice. In this study, we have monitored histological changes in the tumors during 9NC-induced regression, and perturbations in the cell cycle of cells derived from these tumors using flow cytometry. In vivo, 9NC treatment induces dramatic changes in the tumor cells, which die by apoptosis and are ultimately eliminated from the normal tissue. In vitro, 9NC treatment resulted in apoptosis and cytostasis of the NSCLC and SCLC cells, respectively. Further, 9NC induced cytostasis in control, normal human lung fibroblasts. Therefore, the studies in vivo have indicated that 9NC acquires a remarkable antitumor activity against both the SCLC and NSCLC types tested, and that results of studies in vitro may not reflect the results observed in vivo.
Han
Z
Z
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA.
Wyche
J H
JH
Sands
H
H
Pantazis
P
P
D000818:Animals; D017209:Apoptosis; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008168:Lung / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
C079905:rubitecan; D002166:Camptothecin