The action of 5-fluorouracil on human HT29 colon cancer cells grown in SCID mice: mitosis, apoptosis and cell differentiation

Abstract

Summary This study investigates the effects of the anti-metabolite 5-fluorouracil (5-FU) on the human colon cancer line HT29 (107 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 Nacetylgalactosamine 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.

Hyaluronic acid–nimesulide conjugates as anticancer drugs against CD44-overexpressing HT-29 colorectal cancer in vitro and in vivo

“…Mice that received 50 mg/kg 5-FU once per week through the lateral tail vein acted as the positive control group. 55,56 Tumor size and body weight were recorded for each mouse every 3 or 4 days. The percentage of tumor growth inhibition (TGI %) was calculated from the relative tumor volume at day 24.…”

SCID mouse models to study human cancer pathogenesis and approaches to therapy: potential, limitations, and future directions

“…SCID mice engrafted with human tumors have been used extensively to evaluate conventional as well as novel chemotherapeutic agents (65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75). Several important variables exist among these studies.…”

Drug-induced Apoptosis and p53, BCL-2 and BAX Expression in Breast Cancer Tissues In Vivo and in Fibroblast Cells In Vitro

“…The prevention of DNA replication due to unrep aired DNA lesion results in disruption of integrated cell cycle events, which can trigger the apoptotic cascade (33,34) . Wh ile several authors have observed that 5-FU can induce apoptosis (32)(33)(34)(35)(36)(37)(38), the precise molecular signals that underlie this process are not fully characterized. In this work, we evaluated apoptosis and p53, BCL-2 and BAX expression in surgical specimens of breast cancer with and without preoperati ve 5'-DFUR treatment.…”