Hasuda K, Kobayashi H, Taniguchi S, Baba T
Department of Experimental Cell Research, Kyusyu University, Fukuoka, Japan.
Cancer Lett. 1990 Nov 5;54(3):133-7. doi: 10.1016/0304-3835(90)90034-u.
We previously reported that the cytotoxicity of carboquone (CQ) was potentiated in vitro and in vivo under acidic conditions. In this study, an acidic vehicle adjusted with lactate at various low pHs was used for CQ intra-arterial (i.a.) injection, in order to enhance the antitumor effects of i.a. CQ chemotherapy. Treatments were evaluated in Wistar/KA rats bearing a limb tumor 5 days after the inoculation of 3 x 10(6) syngeneic RBT-1 tumor cells into the hind limb. In chemotherapy experiments using an intrafemoral injection of CQ at 1.5 mg/kg in phosphate-buffered saline (PBS, pH 7.4) or in an acidic vehicle at pH 5.0 or 6.0, the antitumor effects seen in rats given CQ in acidic vehicles, evaluated by tumor weight 14 days after treatment, were significantly greater than that seen in rats given CQ in PBS. There were no significant differences either in changes of body weight or in the number of leukocytes after treatment between the groups given CQ in PBS and in an acidic vehicle at pH 6.0. Although in the group given CQ at 2.0 mg/kg in PBS, the antitumor effect was the same as that observed in rats given CQ at 1.5 mg/kg in an acidic vehicle at pH 6.0, the side effects observed in the former group were much severer than in the latter group. These data suggest that the antitumor effect of i.a. CQ chemotherapy can be potentiated by using an acidic vehicle.
我们之前报道过，在酸性条件下，卡波醌（CQ）的细胞毒性在体外和体内均会增强。在本研究中，使用在不同低pH值下用乳酸调节的酸性载体进行CQ动脉内（i.a.）注射，以增强i.a. CQ化疗的抗肿瘤效果。将3×10(6) 同基因RBT-1肿瘤细胞接种到后肢5天后，在患有肢体肿瘤的Wistar/KA大鼠中评估治疗效果。在化疗实验中，以1.5 mg/kg的剂量在磷酸盐缓冲盐水（PBS，pH 7.4）或pH 5.0或6.0的酸性载体中股动脉内注射CQ，通过治疗后14天的肿瘤重量评估，在酸性载体中给予CQ的大鼠中观察到的抗肿瘤效果明显大于在PBS中给予CQ的大鼠。在PBS和pH 6.0的酸性载体中给予CQ的组之间，治疗后体重变化或白细胞数量均无显著差异。虽然在PBS中给予2.0 mg/kg CQ的组中，抗肿瘤效果与在pH 6.0的酸性载体中给予1.5 mg/kg CQ的大鼠中观察到的相同，但前一组观察到的副作用比后一组严重得多。这些数据表明，使用酸性载体可以增强i.a. CQ化疗的抗肿瘤效果。
