腺病毒介导siCD44实验性治疗人CNE-2L2鼻咽癌

Experimental siCD44-targeted Therapy of Human Nasopharyngeal Carcinoma Mediated by Adenovirus

目的探讨用siCD44治疗实体瘤的可能性。方法以高表达CD44的人鼻咽癌细胞CNE-2L2为研究对象,用软琼脂集落形成实验和细胞接种裸鼠后成瘤性生长及肿瘤肺转移检测细胞恶性生物学行为。构建Ad5-siCD44,用293细胞包装产生病毒。接种CNE-2L2细胞于裸鼠皮下,待肿瘤长到50～100mm3大小,瘤体内注射Ad5-siCD44,以注射PBS或Ad5-egfp为对照,2周后比较肿瘤的大小和重量。结果CD44表达抑制致细胞的恶性生物学行为明显受抑。瘤体内注射PBS、Ad5-egfp和Ad5-siCD442周后,肿瘤的平均体积分别为(3.139±0.850)、(3.612±0.888)和(1.512±0.742)cm3,实验组与对照组相比差异有显著性(P<0.05)。3组的平均瘤重分别为(2.28±0.73)、(1.83±0.26)和(1.20±0.64)g,实验组与对照组相比差异有显著性(P<0.05)。结论瘤体内注射Ad5-siCD44对CD44高表达的鼻咽癌细胞CNE-2L2所生成的肿瘤有一定治疗作用。

Objective To explore the possibility of treating solid tumor with siCD44. Methods Human nasopharyngeal carcinoma cell CNE-2L2 with high expression of CD44 was used in this study. The malignant activities of cells were examined by colony formation test, tumorigenesis, and lung metastasis of the tumor in nude mice. Ad5-siCD44 was constructed and adenoviruses were produced in 293 cells. CNE-2L2 cells were subcutaneously inoculated into nude mice. When tumors grew to 50-100 mm^3 , Ad5-siCD44 was injected into tumors, and Ad5-egfp and PBS were also injected as controls. The size and weight of tumors were compared after 2 weeks. Results Suppression of CD44 expression profoundly inhibited the malignant activities of CNE-2L2 cell. The average sizes of the tumors were （3. 139 ±0. 850）, （3. 612 ±0. 888）, and （ 1. 512 ±0. 742） cm^3 after the intra-tumor injection of PBS, Ad5-egfp, and Ad5-siCD44, respectively, after two weeks. Significant difference was found between Ad5-siCD44 group and control groups （ P 〈 0.05 ）. The average weights were （2.28 ± 0.73）, （ 1.83 ± 0.26）, and （ 1.20 ± 0.64） g, respectively, and significant difference was also found between AdS-siCD44 group and control groups （ P 〈 0.05 ）. Conclusion Intra-tumor injection of AdS-siCD44 can exhibit the therapeutic effect on the tumor inoculated with CNE-2L2 cells with high expression of CD44 in nude mice.