Formulation Comprising Arsenic Trioxide and Dimercaprol Enhances Radiosensitivity of Pancreatic Cancer Xenografts

Abstract

Objective: To investigate the efficacy of a formula comprising arsenic trioxide and dimercaprol (BAL-ATO) as a radiosensitizing agent in model mice with pancreatic cancer xenografts. Methods: Female BALB/c nude mice bearing SW1990 human pancreatic cancer xenografts were divided into four treatment arms, including control, radiotherapy (RT), BAL-ATO, and RT + BAL-ATO groups. Survival and tumor volume were analyzed. We also assessed apoptosis in tumor samples by live imaging and detected hypoxia by confocal laser microscope observation. We further investigated the mechanisms of BAL-ATO action in RT by detecting affected proteins by western blot and immunohistochemistry assays. Results: Median survival was significantly longer in the RT + BAL-ATO group (64.5 days) compared with the control (49.5 days), RT (39 days), and BAL-ATO (48 days) groups ( P < 0.001). RT + BAL-ATO inhibited the growth of tumors in mice by 73% compared with the control group, which was significantly higher than the rate of inhibition following RT alone (59%) ( P < 0.01). Further analysis showed an improved microenvironment in terms of hypoxia in tumors treated with BAL-ATO alone or RT + BAL-ATO. Expression of signaling molecules associated with pancreatic cancer stem cells, including CD24, CD44, ALDH1A1, Gli-1, and Nestin, was detected in tumors treated with BAL-ATO alone or in combination with RT. Conclusion: These data suggest that BAL-ATO function as a radiosensitizer in mice with pancreatic cancer xenografts, via mechanisms involving hypoxia reduction and inhibition of signaling pathways associated with pancreatic cancer stem cells. BAL-ATO may thus be a promising radiosensitizing agent in patients with pancreatic cancer.

Trace elements in pancreatic cancer

“…In addition to gemcitabine, ATO can also overcome the resistance of PCACs to erlotinib, 96 thereby enhancing the effect of erlotinib on APCA. ATO also functions as a sensitizer in radiotherapy for PCA, 97 and its mechanism may involve reversing the hypoxic environment and downregulating CD24 and CD44. Coincidentally, CD24 and CD44 have been identified as being characteristically expressed in PCA stem cells 98 .…”

Principles and Applicability of Integrated Remediation Strategies for Heavy Metal Removal/Recovery from Contaminated Environments

“…HM ions are actively removed from plants by excluders, which make up the majority of plant species capable of living in soils high in dangerous trace elements (Sun et al 2022;Tang et al 2021Tang et al , 2022. An HM ion is only toxic to the roots of an excluder plant, while the aerial parts are mainly unaffected by the toxin.…”

“…During World War II, dimercaprol (also known as British Anti-Lewisite or BAL) was created as a test antidote to the arsenic-based poison gas Lewisite (BAL). As a result of their work painting the hulls of ships following World War II, many navy personnel suffered lead poisoning (Tang et al 2021(Tang et al , 2022. This was the first time EDTA had been used medically to chelate lead.…”