【摘要】 目的 研究放线菌素D(Actinomycin D,ACTD)和替尼泊苷(Teniposide,VM-26)对大鼠胶质瘤细胞增殖的体内治疗效果。
方法 将野生型的C6鼠胶质瘤细胞接种于鼠脑右侧尾状核(对照组10只,空载组10只),并对鼠脑内已形成的C6胶质瘤分别用ACTD及VM-26抗瘤缓释剂瘤区原位注射(治疗组各10只)。观察各组大鼠的一般情况、生存期、肿瘤病理学和磁共振成像(MRI)动态改变,采用PCNA计数、TUNEL法检测肿瘤细胞增殖活性及凋亡。
结果 对照组及空载组大鼠平均生存期为19.3天,ACTD组6只及VM-26组3只大鼠生存期明显延长,存活期超过200天;除因病理检查人为处死各2只外,ACTD组治疗后4周内死亡2只,VM-26组5只。MRI检查对照组大鼠脑内有明显瘤灶,治疗组大鼠脑内瘤灶治疗后明显减少或消失,均与病理学检查结果一致,而且治疗组大鼠C6细胞增殖活性降低,大量细胞凋亡,ACTD较VM-26显著。
结论 ACTD可望成为体内局部应用治疗胶质瘤的优选化疗药物。
【关键词】 放线菌素D;替尼泊苷;神经胶质瘤;体内;化疗
Therapeutic effect of ACTD and VM-26 on rat C6 glioma in vivo
WU Yong-Kang,DONG Lun,LIU Hua-wei,et al.Department of Neurosurgery,Clinical Medical Hospital of Yangzhou University,Yangzhou 225001,China
【Abstract】 Objective To study the therapeutic effect of ACTD and VM-26 on rat C6 glioma in vivo.
Methods Wild type C6 cells were implanted stereotaxically to the caudate nucleus of right cerebrum of Wistar rats(control and empty loading group,10 rats respectively),and rats with cerebral tumor foci were treated ACTD and VM-26 mediated by delayed release retarder (treated group,10 rats respectively).The general manifestation,survival time,MRI features,histopathological change,proliferation activity and apoptosis of the glioma in each group of rats were observed.
Results The mean survival time of control animals was 19.3 days.Two ACTD or VM-26 treated rats were killed on day 28 and 58 after implantation for histopathological examination.The surviving time of the 9 remaining rats(6 ACTD and 3 VM-26 treated rats)was over 200 days.MRI demonstrated a distinct cerebral tumor in control rats,but the tumor foci were disappeared almost completely in the treated rats.The cerebral glioma of rats after the treatment with ACTD showed decrease in proliferation activity and apoptosis,significantly decrease than the treatment with VM-26.
Conclusion The results of ACTD in treatment of rat C6 glioma is encouraging.It can be used as the chemotherapy for human malignant glioma.
【Key words】 ACTD;VM-26;glioma;in vivo;chemotherapy
我们以往的研究结果表明,放线菌素D(Actinomycin D,ACTD)可显著抑制C6鼠胶质瘤细胞恶性增殖诱导细胞凋亡,在4个不同的浓度对比中ACTD的抑瘤作用均强于替尼泊苷(Teniposide,VM-26),凋亡率在大剂量ACTD时的作用明显优于VM-26[1]。为进一步明确二者对恶性胶质瘤化疗疗效,我们研究了C6细胞接种于鼠脑的致瘤性以及对鼠脑内已形成瘤灶的C6胶质瘤应用ACTD及VM-26的抗瘤缓释剂瘤区原位治疗的疗效,观察大鼠的一般情况、生存期、肿瘤体积变化以及肿瘤病理组织学与细胞生物学特征变化。
1 材料与方法
1.1 实验材料 C6鼠胶质瘤细胞系由中国科学院动物所提供。细胞培养基:DMEM (Dulbecco modifi
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