Rb94基因联合放射治疗对荷瘤裸小鼠食管癌细胞生长的抑制作用

Inhibitory effect of Rb94 gene combined with radiotherapy on growth of esophageal carcinoma cells of tumor-bearing nude mice

目的:探讨人视网膜母细胞瘤Rb94基因联合电离辐射对荷瘤裸小鼠食管癌细胞生长的抑制作用,阐明Rb94基因与放射治疗(放疗)抑制肿瘤细胞生长的协同作用。方法:将食管癌K150细胞接种于BALB/c-nu裸小鼠建立肿瘤模型。实验分为对照组(未进行处理)、Ad-LacZ组(为含LacZ基因但不含Rb94基因的对照腺病毒,分别于0、3和7d以Ad-LacZ感染瘤体)、Ad-Rb94组(分别于0、3和7d以Ad-Rb94感染瘤体)、照射组(分别于1、4和8d进行4Gyγ射线局部照射瘤体)和Ad-Rb94联合照射组(联合组,Ad-Rb94感染后进行4Gyγ射线局部照射瘤体)。检测各组小鼠食管癌瘤体体积、瘤体质量、肿瘤生长抑制率和肿瘤组织中ABL及JNK的表达水平,并对肿瘤组织进行病理学分析。结果:与对照组比较,Ad-Rb94组、照射组和联合组裸小鼠肿瘤生长速度缓慢,肿瘤生长出现抑制效应;治疗第15天联合组小鼠肿瘤体积明显小于Ad-Rb94组和照射组,与对照组和Ad-LacZ组比较差异有统计学意义(F=26.7,F=23.8,P<0.01)。治疗结束后联合组小鼠瘤体质量最轻,肿瘤生长抑制率高达81.16%,明显高于Ad-Rb94组(57.84%)和照射组(38.20%)(P<0.01)。与对照组比较,联合组小鼠肿瘤组织中ABL和JNK的表达水平明显升高(P<0.01)。与其他组比较,联合组肿瘤细胞有较少的核分裂和较浅的核深染。结论:Rb94基因联合放疗对荷瘤裸小鼠肿瘤的生长抑制具有协同作用。

Objective：To study the inhibitory effect of retinoblastoma 94（Rb94）gene combined with radiotherapy ionizing radiation on the growth of esophageal carcinoma cells of tumor-bearing nude mice,and to clarify the synergistic effect of Rb94 gene and radiotherapy in inhibiting the growth of tumor cells.Methods：The models of tumor-bearing BALB/c-nu nude mice were built by inoculating the K150 cells.The model mice were divided into five groups：blank control（no any treatment）,Ad-LacZ（control adenovirus including LacZ gene but not Rb94 gene,Ad-LacZ was transfered into tumor xenograft on 0,3,7dseparately）,Ad-Rb94（tumor xenograft was transfected with Ad-Rb94 on 0,3,7dseparately）,radiation（tumor xenograft was irradiated with 4 Gyγ-radiation on 1,4,8dseparately）and Ad-Rb94 combined with radiation（combination group,tumor xenograft was irradiated with 4 Gyγ-radiation after transfected with Ad-Rb94）groups.The volumes and the weights of esophageal carcinoma and the inhibitory rates of tumor growth of the mice in various groups were detected.The expression levels of ABL and JNK kinase in tumor tissue of the mice in various groups were measured,and the pathological changes of tumor tissue were investigated.Results：The speeds of tumor growth of the nude mice in Ad-RB94,radiation,and combination groups were slower than that in control group.The volume of esophageal carcinoma in combination group at day 15 after treatment was markedly smaller than those in Ad-RB94 and radiation groups,and there were significant differences compared with control group and Ad-LacZ group（F=26.7,23.8;P〈0.01）.The tumor weight of the nude mice in combination group was the lightest at the end of treatment;the inhibitory rate of tumor growth in combination group reached 81.16%and was significantly higher than those in AdRb94group（57.84%）and radiation group（38.20%）（P〈0.01）.The expression levels of ALB and JNK kinase in tumor tissue of the mice in combination group was markedly higher than those in control group（P〈0.01）.Compared with other groups,the tumor cells in combination group had fewer karyokinesis and lower level of nuclei hyperchromasia.Conclusion：Rb94 gene combined with radiotherapy shows synergistic effect in inhibiting the growth of tumor of tumor-bearing nude mice.