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目的:探讨E1B-55kDa缺陷腺病毒dl1520与顺铂(DDP)联合应用对鼻咽癌的抑制作用。方法:采用MTT法测定体外dl1520联合DDP对鼻咽癌的细胞毒作用;在鼻咽癌裸鼠移植瘤上进行抗瘤实验,并用免疫组化检测腺病毒六邻体抗原的表达,分析dl1520在肿瘤内的复制情况。结果:在体外,dl1520能明显抑制CNE-2鼻咽癌细胞的生长,当感染复数(MOI)为0.032、0.160、0.800、4.000、20.000、100.000时,dl1520对CNE-2细胞的抑制率分别为2.78%、7.41%、10.19%、24.07%、45.37%和67.59%;当同时加入1μg/ml顺铂时,抑制率分别为29.63%、32.41%、40.74%、52.78%、66.67%和74.07%,而单独顺铂对CNE-2的抑制率为24.07%,联合组与单用dl1520组和单用DDP组比较均存在显著差异(P<0.01)。在动物实验中,dl1520单独及联合较低剂量DDP能显著抑制裸鼠移植瘤的生长,抑瘤率分别为35.71%和55.13%,与对照组比较,P值分别小于0.01和0.001;联合组与单独DDP组(抑瘤率为21.65%)比较也存在显著差异(P<0.05)。免疫组化结果证实,在dl1520组和联合组的肿瘤组织内存在大量腺病毒的复制,而对照组和DDP组中未见。结论:E1B-55kDa缺陷腺病毒dl1520对鼻咽癌具有一定的抑制作用,而dl1520与DDP联合应用可显著增强其抗癌效果。
Objective: To investigate the inhibitory effect of combined application of E1B-55kDa deficient adenovirus dl1520 and cisplatin (DDP) on nasopharyngeal carcinoma. METHODS: MTT assay was used to determine the cytotoxicity of dl1520 combined with DDP in nasopharyngeal carcinoma. Anti-tumor experiments were performed on nude mice transplanted tumor of nasopharyngeal carcinoma. The expression of adenovirus hexon antigen was detected by immunohistochemistry and the dl1520 was analyzed. Intratumoral replication. RESULTS: In vitro, dl1520 significantly inhibited the growth of CNE-2 nasopharyngeal carcinoma cells. When the multiplicity of infection (MOI) was 0.032, 0.160, 0.800, 4.000, 20.000, and 100.000, the inhibition rates of dl1520 on CNE-2 cells were 2.78%, 7.41%, 10.19%, 24.07%, 45.37%, and 67.59%; when 1 μg/ml cisplatin was added at the same time, the inhibition rates were 29.63%, 32.41%, 40.74%, 52.78%, 66.67%, and 74.07%, respectively. The inhibition rate of CNE-2 by cisplatin alone was 24.07%, and there was significant difference between the combination group and the dl1520 group alone and the DDP group alone (P<0.01). In animal experiments, dl1520 alone or in combination with lower doses of DDP significantly inhibited the growth of xenografts in nude mice. The tumor inhibition rates were 35.71% and 55.13%, respectively. Compared with the control group, the P values were less than 0.01 and 0.001 respectively; The DDP group alone (inhibition rate was 21.65%) also showed significant differences (P<0.05). The results of immunohistochemistry confirmed the presence of a large number of adenovirus replications in the tumor tissues of the dl1520 group and the combined group, but not in the control group and the DDP group. CONCLUSION: The dl1520 deficient adenovirus E1B-55kDa has a certain inhibitory effect on nasopharyngeal carcinoma, and the combination of dl1520 and DDP can significantly enhance its anticancer effect.