Yoshida T, Shimizu K, Ushio Y, Hayakawa T, Mogami H, Sakamoto Y
Gan To Kagaku Ryoho. 1986 Jun;13(6):2141-6.
Reserpine was shown to enhance the cytotoxicity of ACNU in both C6 and C6/ACNU rat glioma cells in vitro and also to enhance the chemotherapeutic effect of ACNU in C6/ACNU-bearing rats (C6/ACNU meningeal gliomatosis rats), in which ACNU resistance could be partially overcome by reserpine. When reserpine was added to the culture at a concentration of 10 microM, the IC50 of ACNU for C6/ACNU cells decreased to the level of that for C6 cells. Intracellular uptake of ACNU in C6/ACNU cells increased and the efflux from the cells decreased when 20 microM reserpine was added to the culture. In in vivo experiments, combined ACNU (1 mg/kg) and reserpine (250 micrograms/kg) therapy by intrathecal injection of these drugs improved % ILS (increased life span) with statistical significance compared with that after treatment with ACNU alone. The probable explanation of the enhanced cytotoxic-effect of ACNU in ACNU-resistant glioma cells presented in in vitro and in vivo is increased intracellular ACNU concentration resulting from inhibition of the efflux of ACNU from the resistant cells.
利血平在体外可增强ACNU对C6和C6/ACNU大鼠胶质瘤细胞的细胞毒性，还可增强ACNU对荷C6/ACNU大鼠（C6/ACNU脑膜胶质瘤大鼠）的化疗效果，其中利血平可部分克服ACNU耐药性。当以10微摩尔/升的浓度将利血平添加到培养物中时，ACNU对C6/ACNU细胞的IC50降至对C6细胞的水平。当向培养物中添加20微摩尔/升利血平时，C6/ACNU细胞中ACNU的细胞内摄取增加，细胞外流减少。在体内实验中，通过鞘内注射联合使用ACNU（1毫克/千克）和利血平（250微克/千克）进行治疗，与单独使用ACNU治疗相比，提高了%ILS（延长寿命），具有统计学意义。体外和体内实验中ACNU对耐药胶质瘤细胞细胞毒性增强的可能解释是，由于抑制了ACNU从耐药细胞中的外流，导致细胞内ACNU浓度增加。
