国际肿瘤学杂志

国际肿瘤学杂志 ›› 2017, Vol. 44 ›› Issue (4): 266-270.doi: 10.3760/cma.j.issn.1673-422X.2017.04.006

• 论著 • 上一篇    下一篇

新Ⅱ型单纯疱疹溶瘤病毒对肺腺癌的杀伤作用

侯玉晓,盛立军,赵春红,张振,何伟娜   

  1. 250031 济南大学 山东省医学科学院医学与生命科学学院（侯玉晓）；山东省医学科学院附属医院内五科（侯玉晓、盛立军、赵春红、张振、何伟娜）
  • 出版日期:2017-04-08 发布日期:2017-05-09
  • 通讯作者: 盛立军 E-mail:shenglijun328@126.com

Effect of a novel oncolytic herpes simplex virus type Ⅱ on lung adenocarcinoma

Hou Yuxiao, Sheng Lijun, Zhao Chunhong, Zhang Zhen, He Weina   

  1. School of Medicine and Life Sciences, University of Ji′nanShandong Academy of Medical Sciences; Fifth Department of Internal Medicine, Affiliated Hospital of Shandong Academy of Medical Sciences, Ji′nan 250031, China
  • Online:2017-04-08 Published:2017-05-09
  • Contact: Sheng Lijun E-mail:shenglijun328@126.com

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摘要： 目的 建立Lewis肺腺癌C57BL/6小鼠皮下移植瘤模型，观察新Ⅱ型单纯疱疹溶瘤病毒（oHSV2）、顺铂（DDP）以及联合用药对荷瘤小鼠皮下移植瘤体积、中位生存期以及体重的影响。方法 建立Lewis肺腺癌小鼠皮下移植瘤模型。采用随机数字表法将荷瘤小鼠随机分为对照组、oHSV2组、DDP组、oHSV2/DDP序贯组、DDP/oHSV2序贯组、oHSV2＋DDP组，每组12只。每3天测量小鼠肿瘤长短径以及小鼠体重的变化。结果 药物治疗的第21天时，荷瘤小鼠肿瘤体积分别为对照组（1.82±0.06）cm3、oHSV2组（0.63±0.05）cm3、DDP组（0.58±0.03）cm3、oHSV2/DDP序贯组（0.49±0.05）cm3、DDP/oHSV2序贯组（0.42±0.04）cm3，组间差异有统计学意义（F=1 359.01，P=0.000），oHSV2＋DDP组因小鼠过早死亡不予考虑，对照组与oHSV2组(P=0.000)、对照组与DDP组(P=0.000)、对照组与oHSV2/DDP序贯组(P=0.000)、对照组与DDP/oHSV2序贯组(P=0.000)、oHSV2组与DDP组(P=0.017)、DDP与DDP/oHSV2序贯组(P=0.000)、oHSV2/DDP序贯组与DDP/oHSV2序贯组(P=0.001)之间的差异均有统计学意义；荷瘤小鼠的体重分别为对照组（21.64±0.40）g、oHSV2组（21.34±0.37）g、DDP组（15.96±0.43）g、oHSV2/DDP序贯组（19.04±0.31）g、DDP/oHSV2序贯组（16.34±0.30）g，组间差异有统计学意义（F=588.67，P=0.000），对照组与oHSV2组(P=0.076) 之间的差异无统计学意义，对照组与DDP组(P=0.000)、对照组与oHSV2/DDP序贯组(P=0.000)、对照组与DDP/oHSV2序贯组(P=0.000)、oHSV2组与DDP组(P=0.000)、oHSV2组与oHSV2/DDP序贯组(P=0.000)、DDP与DDP/oHSV2序贯组(P=0.013)、oHSV2/DDP序贯组与DDP/oHSV2序贯组(P=0.000)之间的差异均有统计学意义。荷瘤小鼠中位生存期分别为对照组23 d、oHSV2组32 d、DDP组30 d、oHSV2/DDP序贯组37 d、DDP/oHSV2序贯组39 d、oHSV2＋DDP组16 d，组间差异有统计学意义（χ2=120.81，P=0.000），对照组与oHSV2组(χ2=10.88，P=0.001)、对照组与DDP组(χ2=10.69，P=0.001)、oHSV2组与DDP/oHSV2序贯组(χ2=10.09，P=0.001)、DDP与DDP/oHSV2序贯组(χ2=9.67，P=0.002)之间的差异均有统计学意义；而oHSV2组与DDP组(χ2=0.00，P=0.996)、oHSV2/DDP序贯组与DDP/oHSV2序贯组(χ2=2.70，P=0.100)之间的差异均无统计学意义。结论 在不影响小鼠体重的前提下，oHSV2明显抑制荷瘤小鼠的肿瘤体积，显著延长小鼠的中位生存期，尤以DDP/oHSV2序贯组最为显著，为肺腺癌新的治疗方法的探索提供了实验基础。

关键词: 溶瘤病毒, 顺铂, 肺肿瘤

Abstract: Objective  To establish the subcutaneous transplantation tumor models with Lewis lung adenocarcinoma in C57BL/6 mice, and to observe the influence of oHSV2, DDP and drug combination on tumor volume, median survival time and weight of tumorburdened mice. Methods Subcutaneous transplantation tumor models were established with Lewis lung adenocarcinoma in tumorburdened mice. Tumorburdened mice were randomly divided into the control group, oHSV2 group, DDP group, oHSV2/DDP sequential group, DDP/oHSV2 sequential group and oHSV2+DDP combination group with 12 rats in each group using the random number table method. The tumor size and weight of mice were measured every 3 days. Results  On the 21st day, the tumor size of tumorburdened mice in every group was as follows: control group (1.82±0.06)cm3, oHSV2 group (0.63±0.05)cm3, DDP group (0.58±0.03)cm3, oHSV2/DDP sequential group (0.49±0.05)cm3, DDP/oHSV2 sequential group (0.42±0.04)cm3, and the difference was statistically significant (F=1 359.01, P=0.000). The data in oHSV2+DDP group were put away because of premature death in mice. The differences were statistically significant between control group and oHSV2 group (P=0.000), control group and DDP group (P=0.000), control group and oHSV2/DDP sequential group (P=0.000), control group and DDP/oHSV2 sequential group (P=0.000), oHSV2 group and DDP group (P=0.017), DDP group and DDP/oHSV2 sequential group (P=0.000), oHSV2/DDP sequential group and DDP/oHSV2 sequential group (P=0.001). The weight of tumorburdened mice in every group was listed as follows: control group (21.64±0.40)g, oHSV2 group (21.34±0.37)g, DDP group (15.96±0.43)g, oHSV2/DDP sequential group (19.04±0.31)g, DDP/oHSV2 sequential group (16.34±0.30)g, and the difference was statistically significant (F=588.67, P=0.000). The difference was not statistically significant between control group and oHSV2 group (P=0.076). However, the differences were statistically significant between control group and DDP group (P=0.000), control group and oHSV2/DDP sequential group (P=0.000), control group and DDP/oHSV2 sequential group (P=0.000), oHSV2 group and DDP group (P=0.000), oHSV2 group and oHSV2/DDP sequential group (P=0.000), DDP group and DDP/oHSV2 group (P=0.013), oHSV2/DDP sequential group and DDP/oHSV2 sequential group (P=0.000). The median survival time of tumorburdened mice in every group was displayed as follows: control group 23 d , oHSV2 group 32 d, DDP group 30 d, oHSV2/DDP sequential group 37 d, DDP/oHSV2 sequential group 39 d, oHSV2＋DDP combination group 16 d, and the difference was statistically significant (χ2=120.81, P=0.000). The differences were statistically significant between control group and oHSV2 group (χ2=10.88， P=0.001), control group and DDP group (χ2=10.69， P=0.001), oHSV2 group and DDP/oHSV2 sequential group (χ2=10.09， P=0.001), DDP group and DDP/oHSV2 sequential group (χ2=9.67， P=0.002). However, the differences were not statistically significant between oHSV2 group and DDP group (χ2=0.00， P=0.996), oHSV2/DDP sequential group and DDP/oHSV2 sequential group (χ2=2.70， P=0.100). Conclusion  On the premise of that the weight of mice is no affected, oHSV2 can inhibit the tumor size and prolong the median survival time of tumorburdened mice effectively, and the effect of DDP/oHSV2 sequential group is the most significant. This article provides an experimental basis for exploring therapeutic methods of lung adenocarcinoma.

Key words: Oncolytic virus, Cisplatin, Lung neoplasms