Related Experiment Videos
Use of arsenic trioxide as an antivascular and thermosensitizing agent in solid tumors
R J Griffin1, S H Lee, K L Rood
1Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, MN 55455, USA. griff007@tc.umn.edu
Abstract:
Arsenic trioxide, As2O3 (ATO), has been found to be an effective chemotherapeutic for acute promyelocytic leukemia but its effect on solid tumors has not been fully explored. In the present report, we describe our observation that ATO is a potent antivascular agent and that it markedly enhances the effect of hyperthermia on tumors. The tumor blood perfusion in SCK tumors of A/J mice and FSaII tumors of C3H mice was significantly suppressed for up to 24 hours after an i.p. injection of 8 mg/kg ATO. ATO was also found to be able to increase the thermosensitivity of tumor cells in vitro. As a probable consequence of these effects, ATO treatment markedly increased the tumor growth delay caused by hyperthermia at 41.5 to 42.5 degrees C. Immunohistochemical staining of tumor tissue revealed that the expression levels of several adhesion molecules and TNFalpha are noticeably increased in tumors 2 to 6 hours after systemic ATO treatment. It is concluded that ATO is potentially useful to enhance the effect of hyperthermia on tumors at a clinically relevant temperature.
Insights
Arsenic trioxide (ATO) effectively targets tumor blood vessels and enhances hyperthermia
Area of Science:
- Oncology
- Cancer Research
- Tumor Biology
Background:
- Arsenic trioxide (ATO) is a known chemotherapy for acute promyelocytic leukemia.
- Its efficacy against solid tumors remains largely uninvestigated.
Purpose of the Study:
- To explore the effects of ATO on solid tumors.
- To investigate ATO's potential to enhance hyperthermia treatment for solid tumors.
Main Methods:
- In vivo studies using SCK and FSaII mouse tumor models.
- In vitro assessment of tumor cell thermosensitivity.
- Immunohistochemical analysis of tumor tissues.
Main Results:
- ATO (8 mg/kg) significantly suppressed tumor blood perfusion for up to 24 hours.
- ATO increased tumor cell sensitivity to hyperthermia (41.5–42.5°C) in vitro.
- ATO treatment combined with hyperthermia significantly increased tumor growth delay.
- Increased expression of adhesion molecules and TNF-alpha was observed in tumors post-ATO treatment.
Conclusions:
- Arsenic trioxide exhibits potent antivascular properties.
- ATO enhances the efficacy of hyperthermia in solid tumors.
- ATO shows potential for clinical application in combination with hyperthermia.