Griffin R J, Lee S H, Rood K L, Stewart M J, Lyons J C, Lew Y S, Park H, Song C W
Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Neoplasia. 2000 Nov-Dec;2(6):555-60. doi: 10.1038/sj.neo.7900123.
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.
三氧化二砷（As₂O₃，ATO）已被发现是治疗急性早幼粒细胞白血病的一种有效化疗药物，但其对实体瘤的作用尚未得到充分研究。在本报告中，我们描述了我们的观察结果：ATO是一种有效的抗血管生成剂，并且它能显著增强热疗对肿瘤的作用。在腹腔注射8mg/kg ATO后，A/J小鼠的SCK肿瘤和C3H小鼠的FSaII肿瘤的肿瘤血液灌注在长达24小时内被显著抑制。还发现ATO能够在体外增加肿瘤细胞的热敏感性。作为这些作用的一个可能结果，ATO治疗显著增加了在41.5至42.5摄氏度热疗引起的肿瘤生长延迟。肿瘤组织的免疫组织化学染色显示，在全身ATO治疗后2至6小时，肿瘤中几种粘附分子和TNFα的表达水平明显增加。得出的结论是，ATO在临床相关温度下增强热疗对肿瘤的作用方面可能是有用的。
