反义survivin联合顺铂抑制裸鼠荷骨肉瘤生长(英文)

Inhibitory effect of survivin antisense oligodeoxyribonucleotide combined with DDP in nude mice bearing human osteosarcoma xenograft

目的:探讨反义基因治疗与化疗联合应用提高骨肉瘤疗效的可行性及其机制。方法:通过构建荷骨肉瘤裸鼠模型,采用瘤内注射和腹腔给药方式,以survivin反义寡核苷酸(ASODN)配合顺铂(DDP)对瘤鼠进行联合干预治疗,并与各单药组进行比较,观测各组裸鼠肿瘤生长情况、评估瘤体病理形态,免疫组织化学法检测瘤组织survivin蛋白表达,DNA末端原位标记法(TUNEL法)检测肿瘤细胞凋亡水平。结果:与各单药组相比,联合治疗组在显著下调survivin蛋白表达同时,肿瘤细胞凋亡坏死更为明显,肿瘤生长受抑效果更强。结论:ASODN对DDP具有明显增效作用,可弥补DDP耐药缺陷,二者联合可望发挥协同抗瘤效应。

AIM： To investigate the feasibility and its mechanisms of improving therapeutic effect by antisense gene therapy combined with chemotherapy in osteosarcoma. METHODS： The human osteosarcoma implanted tumor model in the nude mice was established. By intratumoral injection and abdominal cavity administration, the tumor beating mice were treated with survivin ASODN in combination with diamminedichloroplatinum （DDP） for a week. Comparison with each single - agent therapy and control group was performed in aspects such as tumor growth condition, pathological changes of tumor tissues; survivin protein expression in tumor tissues by immunohistechemistry, survivin mRNA expression levels by RT - PCR method and tumor apoptosis by Tdt - mediated dUTP nick end labeling （TUNEL）. RESULTS： All nude mice survived the therapy. As compared with the control group, the antisense gene therapy group presented synchronous decrease in survivin mRNA and protein expression; all therapy group displayed tumor growth inhibition and cell apoptosis with different extent; while in contrast to single - agent therapy group, the combined therapy group showed stronger inhibition of tumor growth and abundant tumor cell apoptosis with the highest apoptotic rate. CONCLUSION： Synergistic effect was achieved by combination of DDP with ASODN that may overcome drug resistant of DDP and the combined strategy may shed new light on the cancer therapy.