Monzen Hajime, Griffin Robert J, Williams Brent W, Amano Morikazu, Ando Satoshi, Hasegawa Takeo
Department of Radiology, Otsu Red Cross Hospital, 1-35 Nagara, Otsu-shi, Shiga 520-8511, Japan.
Radiat Med. 2004 Jul-Aug;22(4):205-11.
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.
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.
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.
The results suggest that ATO and radiation can enhance the radiosensitivity of solid tumor.
三氧化二砷（ATO）已被报道为治疗急性早幼粒细胞白血病（APL）的有效化疗药物，最近，其在实体瘤中的抗肿瘤作用也得到了证实。然而，关于ATO对实体瘤作用机制的了解却很少。我们研究了ATO的抗血管生成作用以及ATO与放射治疗联合应用的潜力。
我们研究了ATO对C3H小鼠的鳞状细胞癌（SCC）VII小鼠肿瘤的抗血管生成作用和放射增敏作用。使用磁共振成像（MRI）检测抗血管生成作用，通过克隆形成试验和肿瘤生长延迟研究放射敏感性。还用苏木精和伊红（H&E）染色观察了各种治疗后肿瘤的组织病理学变化。
腹腔注射8mg/kg的ATO后，在T2加权成像上观察到动物后肢肿瘤中心区域的坏死和血流变化。与单独的任何一种治疗相比，先给予ATO再进行放射治疗可降低SCC VII细胞的克隆存活能力。单独给予10 - 20Gy放射治疗后的肿瘤生长延迟与对照肿瘤相比略有增加，但在照射20Gy前2小时注射ATO的联合治疗显著延长了肿瘤生长延迟近20天。
结果表明ATO和放射治疗可增强实体瘤的放射敏感性。
