重组腺病毒Ad5F35-SH2-DED对K562细胞裸鼠致瘤能力的影响

目的:研究融合蛋白SH2-DED(SD)对白血病K562细胞裸鼠皮下移植瘤的影响.方法:建立K562细胞裸鼠皮下移植瘤的重组腺病毒预防和治疗模型.预防模型采用皮下注射经重组腺病毒Ad5F35-SD或Ad5F35-SmD预处理的K562细胞；治疗模型采用皮下注射K562细胞建立皮下移植瘤后,进行Ad5F35-SD或Ad5F35-SmD的瘤体内多点注射.观察裸鼠移植瘤的生长情况以及移植瘤肿瘤细胞的形态学变化.应用TUNEL法和电子显微镜观察移植瘤肿瘤细胞的凋亡情况.结果:治疗模型组中,Ad5F35-SD处理组移植瘤体积明显缩小,肿瘤细胞核浓缩,细胞质染色加深.TUNEL法和电子显微镜检测结果提示,肿瘤细胞发生凋亡,且凋亡相关蛋白caspase-3和caspase-8表达上调.Ad5F35-SD在预防模型组中同样具有抑制移植瘤生长的作用.结论:重组腺病毒Ad5F35-SD能够抑制K562细胞在裸鼠体内的致瘤能力以及裸鼠皮下移植瘤的生长,并促进肿瘤细胞凋亡.

Effect of recombinant adenovirus Ad5F35-SH2-DED on tumorigenicity of K562 cells in nude mice

Objective:To investigate the effect of fusion protein SD(SH2-DED) on the K562 leukemia subcutaneous xenografts in nude mice.Methods:The models of K562 leukemia subcutaneous xenografts in nude mice based on pretreatment and treatment with recombinant adenovirus were established.In the pretreatment model,the K562 cells pretreated with recombinant adenoviruse Ad5F35-SD or its mutant Ad5F35-SmD were subcutaneously injected into the nude mice;in the treatment model,the K562 cells were firstly subcutaneously injected into the nude mice to induce the subcutaneous xenografts,and then the recombinant adenoviruse Ad5F35-SD or its mutant Ad5F35-SmD was intratumorally injected into the xenografts.The growth of the subcutaneous xenografts and the morphological changes of the tumor cells were observed.The apoptosis of the tumor cells in subcutaneous xenografts was detected by TUNEL method and observed under a transmission electron microscope.The expression levels of caspase-3 and caspase-8 proteins in the xenografts were examined by immunohistochemistry.Results:In the treatment model,the volume of subcutaneous xenografts was significantly inhibited by Ad5F35-SD treatment,and the pathological results showed nuclear condensation and deep staining of cytoplasm.The apoptosis of tumor cells was confirmed by TUNEL method and transmission electron microscopy.The expressions of apoptosis-associated proteins caspase-3 and caspase-8 were increased.In the pretreatment model,the growth of xenografts was also inhibited by pretreatment with Ad5F35-SD.Conclusion:Recombinant adenovirus Ad5F35-SD can inhibit the tumorigenicity of K562 cells and the growth of tumor xenografts in nude mice,and promote the apoptosis of tumor cells.