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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。
Objective: To investigate the feasibility and mechanism of antisense gene therapy combined with chemotherapy in improving the efficacy of osteosarcoma. Methods: The nude mice models of osteosarcoma were established by intratumoral injection and intraperitoneal injection, and the interventional treatment of tumor mice with ASODN combined with cisplatin (DDP) The tumor growth of nude mice in each group was observed. The pathological morphology of tumor was evaluated. The expression of survivin protein in tumor tissue was detected by immunohistochemical method. The apoptosis of tumor cells was detected by TUNEL method. Results: Compared with the single drug group, the combination therapy group significantly down-regulated the expression of survivin protein, at the same time, the apoptosis and necrosis of tumor cells were more obvious, and the tumor growth inhibition was stronger. Conclusion: ASODN has a synergistic effect on DDP, which can make up for the defects of DDP resistance. The combination of the two is expected to exert a synergistic anti-tumor effect.