The action of 5-fluorouracil on human HT29 colon cancer cells grown in SCID mice: mitosis, apoptosis and cell differentiation.
This study investigates the effects of the anti-metabolite 5-fluorouracil (5-FU) on the human colon cancer line HT29 (10(7) cells per dose) grown subcutaneously in severe combined immunodeficient (SCID) mice. The efficacy of 5-FU was quantitatively evaluated by comparing the tumour weight, mitotic and apoptotic tumour cell indices and the expression of the Ki-67 nuclear antigen in drug-treated animals and control animals. The tumour cell carbohydrates were assessed using a lectin panel. A significant reduction in the tumour weight was found 4 days after initial 5-FU treatment. 5-FU treatment reduced the percentages of mitoses but increased the apoptotic index in the tumour cells. In addition, 5-FU induced an increase in the signet ring cell population and an increased binding for lectins specific for N-acetylgalactosamine and galactose. However, the vast majority of signet ring cells were negative for Ki-67. The results of this study indicate that continuous treatment with 5-FU for 4 days targets metabolic processes relevant for both cell division and apoptosis. The relative increase in the signet ring population can be explained by the fact that the more proliferation-active stem cell population of the tumour is the primary target of the therapy. The lectin-binding patterns reflect these changes and are therefore differentiation linked.
Sharma
R
R
Human Morphology, University of Southampton, UK.
Adam
E
E
Schumacher
U
U
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002240:Carbohydrate Sequence; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D005472:Fluorouracil / Q000494:pharmacology*; D006031:Glycosylation / Q000187:drug effects; D019073:HT29 Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D006651:Histocytochemistry; D006801:Humans; D037102:Lectins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008938:Mitosis / Q000187:drug effects; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D000964:Antimetabolites, Antineoplastic; D037102:Lectins; D005472:Fluorouracil