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目的通过重组逆转录病毒RV-40AS表达bcr-abl反义RNA,激活蛋白激酶PKR引起靶细胞表型改变的策略,研究RV-40AS对K562致瘤裸鼠的抗肿瘤效应。方法建立K562细胞裸鼠移植瘤模型,瘤体注射重组逆转录病毒上清,观察裸鼠瘤体生长状况,于实验终点处死小鼠检测瘤体大小,用western blot检测瘤组织PKR、真核细胞蛋白合成启动因子eIF2α及其磷酸化(p-PKR、p-eIF2α)蛋白质水平。3H-亮氨酸掺入实验检测细胞总蛋白质合成水平。结果RV-40AS作用组裸鼠的瘤体明显小于对照组,瘤重抑制率为61.9%(P<0.05);p-PKR和p-eIF2α蛋白质表达水平有不同程度上调(88%和53%)。3H-亮氨酸掺入实验显示RV-40AS组细胞总蛋白质合成受抑。结论逆转录病毒RV-40AS能激活PKR从而抑制白血病K562细胞移植瘤裸鼠模型的瘤体生长,激活PKR可作为白血病治疗的又一策略。
Objective To investigate the antitumor effect of RV-40AS on the K562 tumorigenic nude mice by expressing the bcr-abl antisense RNA by recombinant retrovirus RV-40AS and activating the protein kinase PKR. Methods The K562 cell xenograft model was established in nude mice. The tumor was injected with the supernatant of recombinant retrovirus. The growth of the tumor was observed. The tumor size was measured at the end of the experiment. The expression of PKR and eukaryotic cells Protein synthesis promoter eIF2α and its phosphorylation (p-PKR, p-eIF2α) protein levels. 3H-leucine incorporation assay to measure total cellular protein synthesis. Results The tumor volume of the nude mice with RV-40AS treatment was significantly lower than that of the control group (61.9%, P <0.05). The protein expressions of p-PKR and p-eIF2α were up-regulated in 88% and 53% . The 3H-leucine incorporation assay showed that total protein synthesis in the RV-40AS group was inhibited. Conclusion Retrovirus RV-40AS can activate PKR and inhibit the growth of nude mice model of K562 cells transplanted with leukemia. Activation of PKR can be used as another strategy for the treatment of leukemia.