Ultrasound therapy for soft tissue sarcoma with new quinolone antibiotics as a sonodynamic compound in vivo

2005年，我们比较了吖啶橙子、吡罗昔康和4种新喹诺酮类抗生素（盐酸洛美沙星、司帕沙星、盐酸环丙沙星、加替沙星水合物）的体外抗肿瘤作用。计算肿瘤细胞与这6种药物的混合物在照射（2 MHz，2.0W，30 s）后的肿瘤细胞存活率。此外，为了指定基团，同时使用D-甘露醇和L-组氨酸。NQ类抗生素在超声辐照下具有抗肿瘤活性。其中司帕沙星（SPFX）的抑瘤作用最强，与L-组氨酸合用可抑制其抑瘤作用。因此，我们认为NQ类抗生素在超声辐照下具有抗肿瘤活性，单线态氧的产生参与了细胞损伤过程。此外，吖啶橙子显示出良好的抗肿瘤作用。2006年，我们在小鼠气囊模型中研究了US与SPFX存在下对肉瘤180细胞的协同抗肿瘤作用。注射肿瘤细胞（1.5 × 10^7）和0.2 mM SPFX溶液后，US（2 MHz，10 W）照射30 s。然而，在SPFX存在下，US的抗肿瘤作用在组织学研究和生存分析中均不明显。应该需要改进超声设备，或开发更好的声动力化合物。吖啶橙子作为一种声动力化合物可能是很有前途的。

In 2005, we compared an antitumor effect of acridine orange, piroxicam, and 4 kinds of New quinolone (NQ) antibiotics (lomefloxacin hydrochloride, sparfloxacin, ciprofloxacin hydrochloride, gatifloxacin hydrate) in vitro. Survival rate of tumor cells of the mixture of tumor cells and these 6 drugs after the irradiation (2 MHz, 2.0 W, for 30 s) was calculated. Furthermore, to specify the radicals, D-mannitol and L-histidine was used concurrently. NQ antibiotics showed antitumor activities under US irradiation. Especially sparfloxacin (SPFX) showed the best antitumor effect, and concurrent use of L-histidine suppressed the effect. Therefore, we considered that NQ antibiotics would be useful compounds for antitumor activities under US irradiation, and generation of singlet oxygen was involved in the cell damage process. In addition, acridine orange showed a good antitumor effect.In 2006, we investigated a synergistic antitumor effect of US in the presence of SPFX against sarcoma 180 cells in mouse air pouch model. After the injection of tumor cells (1.5 x 10^7) and 0.2 mM solution of SPFX, US (2 MHz, 10 W) was irradiated for 30 s. However, an antitumor effect of US in the presence of SPFX was not apparent neither in histological study nor in survival analysis. Improvement of US apparatus, or a development of better sonodynamic compounds should be required. As a sonodynamic compound, acridine orange might be promising.