【摘要】 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。更多还原

【Abstract】 Objective To explore the inhibitory effect of recombinant human adenovirus p53 (rAd-p53) combined with radiotherapy on human hepatocarcinoma in nude mouse model. MethodsNude mice hepatocarcinoma model was established by inoculating SMMC-7721 cells into the back of 18 nude mice. Firstly, two nude mice were taken out randomly, one was administered by intratumoral injection of rAd-p53, another was administered with PBS. After 48 h, the expression of P53 protein was detected by Western blotting. The rest 16 nude mice were divided into 4 groups randomly: the control group, the radiotherapy group, rAd-p53 group and rAd-p53 plus radiotherapy group. The tumor growth curve was plotted and the mice were sacrificed on the 16th day after the treatment and the tumor mass was taked. Meanwhile, the histology of specimens was examined by HE staining. The expression of Ki-67 protein was detected by immunohistochemistry. The apoptotic index was detected by Terminal dUTP nick end labeling (TUNEL) assay. ResultsThe infection of rAd-p53 in SMMC-7721 xenograft was succeeded in the animal model and the expression of P53 protein was increased in 48 h after injection. The tumor inhibitory rate were 81.49%, 30.74% and 33.67% in rAd-p53 plus radiotherapy group, radiotherapy group and rAd-p53 group respectively. Compared to the other groups, the inhibitory rate of rAd-p53 plus radiotherapy group was significantly higher (P<0.01). Tumor necrosis was observed in overall groups and mostly found in rAd-p53 plus radiotherapy group. The Ki-67 expression in the group of rAd-p53 plus radiotherapy was significantly lower than other groups (P<0.01), while the apoptosis index was much higher (P<0.01). ConclusionrAd-p53 combined with radiotherapy can significantly inhibit the growth and enhance radio-sensitivity of hepatocarcinoma in SMMC-7721 xenotransplant in animal model.更多还原