Inhibitory effect of NF-κB p65siRNA on human laryngeal carcinoma xenograft model in nude mice
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摘要: 目的:探讨靶向转录因子NF-κB p65的siRNA对人喉癌裸鼠皮下移植瘤生长的抑制作用。方法:将人喉癌Hep-2细胞注射入裸鼠皮下建立裸鼠移植瘤模型。将15只裸鼠喉癌模型随机分为3组:实验组、阴性对照组与正常对照组,分别给予NF-κB p65siRNA、FAM-Control siRNA和PBS治疗3周。治疗过程中观察肿瘤体积的变化,治疗结束时处死裸鼠,肿瘤称取质量,取肿瘤组织切片进行TUNEL标记及免疫组织化学检测NF-κB p65及Bcl-xL蛋白的表达情况。结果:治疗后实验组平均瘤重(0.53±0.03)g,低于阴性对照组[(0.70±0.04)g]和正常对照组[(0.72±0.07)g],差异有统计学意义(P<0.05);实验组移植瘤体积(1 313.58±114.72)mm3,小于阴性对照组[(1 536.92±80.30)mm3]和正常对照组[(1 661.01±161.84)mm3],差异有统计学意义(P<0.05);实验组NF-κB p65、Bcl-xL蛋白表达水平明显下调,细胞凋亡率增高。结论:siRNA明显抑制了NF-κB p65表达,并抑制肿瘤生长,其机制可能与下调Bcl-xL蛋白表达而诱导细胞凋亡有关。Abstract: Objective:To investigate the inhibitory effect of NF-κB p65siRNA on human laryngeal carcinoma xenograft model in nude mice.Method:Human laryngeal carcinoma cell line Hep-2 was seeded in the subcutaneous layer of 15 nude mice to build laryngeal carcinoma xenograft model.Then they were randomly divided into three groups.NF-κB p65 siRNA was given in siRNA group and FAM-Control siRNA was given in negative control group while phosphstic-buffered saline(PBS) was used in normal control group for 3 weeks.Tumor size and body weight of the mice were measured.TUNEL method and immunohistochemical S-P method were used for detecting the expression of NF-κB p65 and Bcl-xL protein.Result:The volume of tumors in siRNA group was reduced and the average weight of tumors in siRNA group was lower than the other two groups(P<0.05).In siRNA group,the expression of NF-κB p65 and Bcl-xL protein was down-regulated and the apoptotic rate was increased obviously as compared with the negative control group and the normal control group.Conclusion:NF-κB p65siRNA can significantly inhibit the expression of NF-κB p65 and the growth of human laryngeal carcinoma xenograft in nude mice.Its mechanism may be related to inducing the apoptosis in tumor cells by down-regulating the expression of Bcl-xL protein.
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Key words:
- siRNA /
- laryngeal neoplasms /
- NF-κB p65 /
- nude mice
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