NF—κBp65信号通路阻断对小鼠Lewis肺癌细胞凋亡和p65的影响

目的研究p65siRNA抑制NF-κBp65信号通路后，对Lewis肺癌细胞生长的影响。方法采用Lewis肺癌细胞C57雄性小鼠移植瘤组织悬液，建立C57雄性小鼠移植瘤模型。将针对p65的小干扰RNA（smallinterfering RNA，siRNA）接种荷瘤小鼠，观察下调NF—κB／p65表达后荷瘤小鼠瘤细胞凋亡情况；进一步应用荧光定量-PCR和Wstem印迹法检测肿瘤组织中p65mRNA及蛋白表达变化。结果经p65siRNA治疗后，0．05）；TUNEL结果表明，p65siRNA纽肿瘤细胞明显发生凋亡；p65siRNA纽小鼠肿瘤组织p65的mRNA及蛋白表达明显下调。差异均有统计学意义（P〈0．05）。结论NF-κB／p65亚基可能在Lewis肺癌细胞凋亡中发挥重要作用。

Objective To investigate the effects of expression downregulation of nuclear factor-kappaB （NF-KB）/p65 on the growth of tumor and expressions of apoptosis-related genes P65 in nude mouse lung tumour cell xenografts.Methods A nude mouse Lewis lung carcinoma cell xenograft model was established, and the mice were intraperitoneally injected with NF-κB p65 small interfering RNA （siRNA） and sacrificed after 2 weeks of tumour cell injection. Tumour xenografts were harvested for TUNEL, Western blot and quantitative reverse transcription-polymerase chain reaction analyses.Results The TUNEL positive （apoptosis） cells in xenograft sections were 45±5 in PBS and 38±3 in NC siRNA but increased to 271±11 in p65 siRNA-treated mice. Compared to the PBS or the NC mice, levels of P65 mRNA and protein in tumour xenografts were significantly downregulated in p65 siRNA-treated mice.Conclusion Knockdown of NF-KB p65 subunit expression significantly induced tumour cell apoptosis and significantly downregulation of pro-apoptotic protein P65 expression.in P65 siRNA group.Targeting NF-KB p65 subunit expres- sion as a potential therapeutic strategy needs further evaluation in treating human lung cancer.