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Updated: Aug 21, 2026
Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment
Published on: January 7, 2015
Study of arsenic trioxide-induced vascular shutdown and enhancement with radiation in solid tumor
Hajime Monzen1, Robert J Griffin, Brent W Williams
1Department of Radiology, Otsu Red Cross Hospital, 1-35 Nagara, Otsu-shi, Shiga 520-8511, Japan.
Purpose:
Arsenic trioxide (ATO) has been reported to be an effective chemotherapeutic agent for acute promyelocytic leukemia (APL), and, recently, anti-tumor effect has been demonstrated in solid tumors. However, little is known about the mechanism of action of the ATO effect on solid tumor. We investigated the anti-vascular effect of ATO and the potential of combining ATO with radiation therapy.
Materials And Methods:
We studied the anti-vascular effect of ATO and radiosensitization of squamous cell carcinoma (SCC) VII murine tumors of C3H mice. The anti-vascular effect was examined using magnetic resonance imaging(MRI), and radiosensitivity was studied by clonogenic assay and tumor growth delay. Histopathological changes of the tumors after various treatments were also observed with hematoxylin and eosin (H&E) staining.
Results:
Necrosis and blood flow changes in the central region of tumors in the hind limbs of the animals were observed on T2-weighted imaging after an i.p. injection of 8 mg/kg of ATO alone. ATO exposure followed by radiation decreased the clonogenic survival of SCC VII cells compared with either treatment alone. Tumor growth delay after 10-20 Gy of radiation alone was increased slightly compared with control tumors, but the combination of ATO injection 2 hours before exposure to 20 Gy of radiation significantly prolonged tumor growth delay by almost 20 days.
Conclusion:
The results suggest that ATO and radiation can enhance the radiosensitivity of solid tumor.
Insights
Arsenic trioxide (ATO) combined with radiation therapy significantly enhances the anti-tumor effect on solid tumors. This combination therapy improves tumor growth delay and cancer cell death, offering a promising strategy for cancer treatment.
Area of Science:
- Oncology
- Radiation Oncology
- Vascular Biology
Background:
- Arsenic trioxide (ATO) is an effective treatment for acute promyelocytic leukemia (APL).
- ATO has demonstrated anti-tumor effects in solid tumors, but its mechanism is not fully understood.
- Investigating ATO's anti-vascular effects and its synergy with radiation is crucial for solid tumor treatment.
Purpose of the Study:
- To investigate the anti-vascular effect of arsenic trioxide (ATO) on solid tumors.
- To evaluate the potential of combining ATO with radiation therapy for enhanced anti-tumor efficacy.
- To explore the mechanism of ATO-induced radiosensitization in squamous cell carcinoma (SCC).
Main Methods:
- Studied the anti-vascular effects and radiosensitization of ATO in SCC VII murine tumors.
- Utilized magnetic resonance imaging (MRI) to assess tumor vascularity.
- Employed clonogenic assays and tumor growth delay studies to measure radiosensitivity.
- Analyzed histopathological changes using hematoxylin and eosin (H&E) staining.
Main Results:
- ATO treatment alone induced tumor necrosis and altered blood flow in SCC VII tumors.
- Combined ATO and radiation therapy significantly reduced SCC VII cell survival compared to monotherapy.
- The combination of ATO followed by radiation therapy markedly prolonged tumor growth delay by approximately 20 days.
Conclusions:
- Arsenic trioxide (ATO) exhibits anti-vascular effects in solid tumors.
- ATO enhances the radiosensitivity of solid tumors when combined with radiation therapy.
- This combination strategy holds promise for improving solid tumor treatment outcomes.
