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直接转导单纯疱疹病毒胸苷激酶基因对大肠肿瘤的杀伤作用

The killing of colorectal carcinoma by herpes simplex thymidine gene transduction in a nude mouse model
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摘要 目的 通过单纯疱疹病毒胸苷激酶 (HSV tk)基因对荷大肠癌裸鼠肿瘤的直接转导及杀伤作用研究 ,建立有效的自杀基因抑制大肠肿瘤的治疗方法。方法 脂质体法将含HSV tk基因的逆转录病毒载体LNtk及空载体G1Na在Psi 2、PA3 17包装细胞中进行交叉包装、收获病毒上清。4 0只BALB/C裸鼠分成 4组并皮下注射LoVo细胞成瘤 ,将含tk和G1Na的病毒上清分别直接注射到 2组大肠肿瘤部位并予以腹腔注射 3 0 0mg/kg体重环氧鸟苷 (GCV) ;另 2组为未转基因对照组 ,其中予以腹腔注射GCV 1组 ,予以腹腔注射生理盐水 1组。治疗结束后将标本制成石蜡切片进行病理学分析。实验数据的统计学处理采用组间t检验。结果 各组动物成瘤性无明显差异。治疗结束时肿瘤标本的重量分别为 :转tk基因且予以GCV治疗组 (94±5 )mg,转空载体予GCV治疗组 (1687± 3 15 )mg,未转基因予以GCV治疗组动物 (1684± 3 0 1)mg,未转基因予以生理盐水腹腔注射组(164 9± 2 82 )mg,实验组肿瘤与各对照组相比 ,不仅观察到明显的肿瘤杀伤作用 (均为P <0 .0 1,n=10 ) ,而且存在明显的病理学改变。结论 HSV tk自杀基因有望成为大肠癌辅助治疗的有效手段之一。 Objective To investigate effective ways to inhibit colorectal carcinoma through tk/GCV system in situ. Method The retroviral vector LNtk containing tk gene and control vector G1Na were packaged in Psi 2 and PA317 cells to obtain the supernatant of recombinant retrovirus. 40 male BALB/C nude mice of four week old were dividided into 4 groups at random and implanted LoVo cells to form the tumors. The supernatant of tk gene and G1Na was injected directly into the tumor foci of 2 groups of animals and GCV was administrated intraperitoneally (i.p). The other 2 control groups were given saline and GCV i.p. respectively. At the end of the experiment, animals were sacrificed and the specimens were processed for histopathological analysis. Results Treatment of GCV to tk transfected tumors produced a significant antitumor effect compared to the control ( P <0 01), and at the end of treatment of GCV.Tumors modified by tk gene, tumors modified by G1Na, unmodified tumors and untreated tumors weighed (94±5) mg, (1 687±315) mg, (1 684±301) mg and (1 649±282) mg, respectively. Furthermore, tumors treated with GCV revealed different histopathological features compared with the control tumors. Conclusion HSV tk gene could be a potential tool for the treatment of colorectal carcinomas.
出处 《中华普通外科杂志》 CSCD 2000年第2期102-104,共3页 Chinese Journal of General Surgery
基金 国家自然科学基金!(基金号 3 96 0 0 14 2 )
关键词 单纯疱疹病毒 胸苷激酶 大肠肿瘤 自杀基因 Herpers simplex virus Thymidine kinase Gene Colorectal neoplasm
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参考文献2

  • 1Wei M X,Cancer Res,1998年,58卷,3529页
  • 2崔龙,中华外科杂志,1998年,36卷,702页
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