Anti-tumor effects of 25-hydroxycholesterol and low-dose recombinant tumor necrosis factor-alpha on rat liver tumorigenesis: modulated differentiation therapy for hepatocellular carcinoma.

  • Authors:
    • S Yokoyama
    • F Nozawa
    • S Tanaka
    • S Muneyuki
    • M Ogawa
  • View Affiliations

  • Published online on: May 1, 2000     https://doi.org/10.3892/ijo.16.5.1029
  • Pages: 1029-1062
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Abstract

Previously, we have demonstrated that treatment of rat AH136B ascites hepatoma cells with 25-hydroxycholesterol (25-OH) induces apoptosis. In this study, to elucidate whether modulated differentiation therapy may be useful in treating patients with hepatoma, we assayed the effects of 25-OH and/or tumor necrosis factor-alpha (TNF) on rat AH136B ascites hepatoma cells in vivo. Here we show that a high concentration of TNF (250 U/ml) mediated a stronger cytocidal effect than a low concentration of TNF (25 U/ml) in vitro. Flow cytometric DNA analysis also showed that treatment of cells with the high concentration of TNF (250 U/ml) increased the percentage of AH136B cells in the G0/G1 phase, while 25 U/ml of TNF did not cause any marked change in cell kinetics. In in vivo experiments, 25-OH (80 microg/rat) and TNF (500 U/rat) were administered after transplanting AH136B cells into Donryu rats intraperitoneally. We found that tumor development was completely inhibited by this treatment in 3 of 9 rats, and their 40-day survival rate was 44%; in contrast, rats administered 25-OH (80 microg/rat) alone or TNF (500 U/ml) alone developed peritonitis carcinomatosa, and died within 13 days of inoculation. These findings suggest that local combined treatment with 25-hydroxycholesterol and low-dose TNF can induce synergistic anti-tumor effects.

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May 2000
Volume 16 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Yokoyama, S., Nozawa, F., Tanaka, S., Muneyuki, S., & Ogawa, M. (2000). Anti-tumor effects of 25-hydroxycholesterol and low-dose recombinant tumor necrosis factor-alpha on rat liver tumorigenesis: modulated differentiation therapy for hepatocellular carcinoma.. International Journal of Oncology, 16, 1029-1062. https://doi.org/10.3892/ijo.16.5.1029
MLA
Yokoyama, S., Nozawa, F., Tanaka, S., Muneyuki, S., Ogawa, M."Anti-tumor effects of 25-hydroxycholesterol and low-dose recombinant tumor necrosis factor-alpha on rat liver tumorigenesis: modulated differentiation therapy for hepatocellular carcinoma.". International Journal of Oncology 16.5 (2000): 1029-1062.
Chicago
Yokoyama, S., Nozawa, F., Tanaka, S., Muneyuki, S., Ogawa, M."Anti-tumor effects of 25-hydroxycholesterol and low-dose recombinant tumor necrosis factor-alpha on rat liver tumorigenesis: modulated differentiation therapy for hepatocellular carcinoma.". International Journal of Oncology 16, no. 5 (2000): 1029-1062. https://doi.org/10.3892/ijo.16.5.1029