重组人p53腺病毒增强肝癌放疗敏感性的实验研究

来源 :第三军医大学学报 | 被引量 : 0次 | 上传用户:gaoyyop
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目的观察重组人p53腺病毒(recombinant human adenovirus p53,rAd-p53)联合放疗对肝癌裸鼠移植瘤生长的抑制作用。方法人肝癌细胞SMMC-7721荷瘤裸鼠18只,应用随机数字表法选取2只,1只瘤内注射rAd-p53,另1只注射PBS,注射后48h处死动物取瘤,Western blot方法检测肿瘤P53蛋白表达;其余16只分为4组:对照组、单独放疗(IR)组、重组人p53腺病毒(rAd-p53)治疗组和重组人p53腺病毒+放疗(rAd-p53+IR)联合治疗组。实验治疗第16天处死动物,绘制肿瘤生长曲线;光镜下观察肿瘤治疗后组织形态学变化;免疫组化S-P法检测Ki-67,TUNEL法检测肿瘤细胞凋亡。结果rAd-p53成功感染了肝癌裸鼠移植瘤细胞,并增强肝癌细胞P53蛋白的表达;rAd-p53+IR联合治疗组、IR组和rAd-p53治疗组的肿瘤生长抑制率分别为81.49%、30.74%和33.67%,其中rAd-p53+IR联合治疗组的肿瘤抑制最强(P<0.01)。光镜下观察各治疗组的肿瘤组织均出现坏死,其中rAd-p53+IR联合治疗组肿瘤坏死较多;rAd-p53+IR联合治疗组肿瘤细胞表达Ki-67明显低于对照组、IR组和rAd-p53治疗组(P<0.01),而肿瘤细胞凋亡显著增加(P<0.01)。结论rAd-p53+IR联合治疗较单独放疗能显著抑制肝癌的生长,rAd-p53能增强肝癌对放疗敏感性。 Objective To observe the inhibitory effect of recombinant human adenovirus p53 (rAd-p53) combined with radiotherapy on the growth of hepatocellular carcinoma xenografts in nude mice. METHODS: Twenty-eight human hepatocellular carcinoma SMMC-7721 tumor-bearing nude mice were randomly divided into two groups. One was intratumoral injected with rAd-p53 and the other was injected with PBS. The animals were sacrificed at 48h after injection, and Western blot was used to detect The other 16 were divided into 4 groups: control group, IR group, recombinant adenovirus p53 (rAd-p53) group and recombinant adenovirus plus radiotherapy (rAd-p53 + IR) Combination therapy group. The experimental animals were killed on the 16th day, and the tumor growth curve was drawn. The morphological changes of the tumor were observed under the light microscope. Ki-67 and TUNEL were used to detect the apoptosis of tumor cells by immunohistochemical S-P method. Results rAd-p53 was successfully infected with transplanted hepatocellular carcinoma cells in nude mice and enhanced the expression of P53 protein in hepatoma cells. The tumor growth inhibition rates of rAd-p53 + IR group, IR group and rAd-p53 group were 81.49% 30.74% and 33.67%, respectively, of which rAd-p53 + IR combination had the strongest tumor inhibition (P <0.01). The tumor necrosis appeared in each treatment group under light microscope. The tumor necrosis in rAd-p53 + IR group was more than that in control group. Ki-67 expression in rAd-p53 + IR group was significantly lower than that in control group and IR group And rAd-p53 treatment group (P <0.01), while the apoptosis of tumor cells was significantly increased (P <0.01). Conclusions rAd-p53 + IR can significantly inhibit the growth of hepatocellular carcinoma compared with radiotherapy alone, and rAd-p53 can enhance the radiosensitivity of hepatocellular carcinoma.
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