Kabuto M, Kaye A H, Hill J S, Stylli S S
Department of Neurosurgery, Higginbotham Neuroscience Research Institute and Department of Surgery, Clinical Neuroscience Centre, Royal melbourne Hospital, Melbourne, Australia.
J Clin Neurosci. 1994 Jan;1(1):47-52. doi: 10.1016/0967-5868(94)90010-8.
MX2, a novel lipophilic morpholino anthracycline, has been reported to have superior chemotherapeutic effects to Adriamycin (ADM) against murine and human tumour cells. In this study the chemotherapeutic effect of MX2 against C6 glioma cells in vitro and in vivo was examined as well as the photocytotoxicity of MX2 and the combination effect of MX2 and photodynamic therapy (PDT) in vitro. The drug concentration required for 50% inhibition of cell growth (IC50) of MX2 for C6 glioma cells was 6.5 +/- 1.0 ng/ml, which was lower than for ADM and nitrosourea (ACNU). The growth of C6 glioma cells inoculated intracerebrally in mice was inhibited by intravenous (iv) injection of MX2 at doses ranging from 1.0-3.0 mg/kg suggesting that MX2 may be clinically effective against human malignant gliomas. Mild photocytotoxicity of MX2 against C6 cells in vitro was observed at high concentrations of MX2 illuminated with white light but not red light (> 630 nm). In combination, MX2 and the photosensitizer haematoporphyrin derivative (HpD) resulted in cyto- and photo-toxicity of C6 glioma cells irrespective of whether the cells were treated with MX2 either immediately after red light illumination following incubation with HpD, or at an interval of 24 hours before incubation with HpD. We conclude that MX2 may be clinically useful against malignant glioma alone, and in combination with other therapies such as PDT.
MX2是一种新型亲脂性吗啉代蒽环类药物，据报道其对鼠类和人类肿瘤细胞的化疗效果优于阿霉素（ADM）。在本研究中，检测了MX2对C6胶质瘤细胞的体内外化疗效果，以及MX2的光细胞毒性和MX2与光动力疗法（PDT）在体外的联合效应。MX2对C6胶质瘤细胞50%抑制细胞生长所需的药物浓度（IC50）为6.5±1.0 ng/ml，低于ADM和亚硝基脲（ACNU）。静脉注射（iv）剂量为1.0 - 3.0 mg/kg的MX2可抑制小鼠脑内接种的C6胶质瘤细胞生长，这表明MX2可能对人类恶性胶质瘤具有临床疗效。在高浓度MX2用白光而非红光（>630 nm）照射时，观察到MX2在体外对C6细胞具有轻度光细胞毒性。联合使用时，MX2与光敏剂血卟啉衍生物（HpD）无论细胞是在与HpD孵育后红光照射后立即用MX2处理，还是在与HpD孵育前24小时的间隔期用MX2处理，都会导致C6胶质瘤细胞产生细胞毒性和光毒性。我们得出结论，MX2单独或与PDT等其他疗法联合使用可能对恶性胶质瘤具有临床应用价值。
