三氧化二砷载药微球治疗VX2肝肿瘤兔模型的效果分析

Effect of arsenic trioxide-loaded CalliSpheres beads in the treatment of rabbits with VX2 liver tumor

目的观察经肝动脉导管化疗栓塞术(TACE)中应用载药栓塞微球(CB)加载三氧化二砷(CBATO)对兔VX2肝肿瘤的疗效。方法荷瘤兔采用数字表法随机分为4组:对照组(n=30)、CB组(n=30,空白微球栓塞)、CBATO组(n=30)、常规TACE(cTACE)组(n=30,三氧化二砷碘油栓塞)。各组分别在术后12 h、3 d、7 d、14 d各处死实验兔5只,采用免疫组织化学法检测残瘤区肿瘤细胞增殖指数和凋亡百分比。术后7 d时测量各组肿瘤坏死体积,并计算肿瘤细胞生长率和坏死率。各组随机抽取10只,用于生存期观察。计量资料多组间比较采用方差分析,进一步两两比较采用LSD-t检验;生存期以Kaplan-Meier生存分析法进行评估,采用log-rank进行检验。结果术后7 d,CBATO组肿瘤细胞生长率明显低于cTACE组、CB组、对照组(P值均<0.05);肿瘤坏死率明显高于其他3组(P值均<0.05)。术后各时间点,CBATO组增殖指数和凋亡百分比与其他3组相比,差异均具有统计学意义(P值均<0.05)。CBATO组、CB组、cTACE组及对照组中位生存时间分别为26、18.5、22、15.5 d,CBATO组实验兔生存时间较其他3组延长(χ^2值分别为3.95、8.99、13.47,P值分别为0.049、0.003、<0.01)。结论CBATO治疗兔VX2肝肿瘤疗效优于cTACE、CB,可明显提高肿瘤的坏死率,促进肿瘤细胞的凋亡,延长实验动物的生存期。

Objective To investigate the effect of arsenic trioxide-loaded CalliSpheres beads(CBATO)in transarterial chemoembolization(TACE)in the treatment of rabbits with VX2 liver tumor.Methods A total of 120 tumor-bearing rabbits were divided into control group,CalliSpheres beads(CB)group(blank beads for TACE),CBATO group,and conventional TACE(cTACE)group(arsenic trioxide lipiodol for TACE)using a random number table,with 30 rabbits in each group.Five rabbits in each group were sacrificed at 12 hours and on days 3,7,and 14 after TACE,and immunohistochemistry was used to measure the proliferation index and apoptosis percentage of tumor cells in the residual tumor area.The tumor necrotic volume was measure on day 7 after TACE,and the growth rate and necrosis rate of tumor cells were calculated.Ten rabbits were randomly selected from each group for the observation of survival time.An analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups;the Kaplan-Meier survival analysis was used to evaluate survival time,and the log-rank test was used for comparison.Results On day 7 after TACE,the CBATO group had a significantly lower growth rate and a significantly higher necrosis rate of tumor cells than the cTACE group,the CB group,and the control group(all P<0.05).At each time point after TACE,there were significant differences in the proliferation index and apoptosis percentage of tumor cells between the CBATO group and the other three groups(all P<0.05).The median survival time was 26 days in the CBATO group,18.5 days in the CB group,22 days in the cTACE group,and 15.5 days in the control group,and the CBATO group had a significantly longer survival time than the other three groups(χ^2=3.95,8.99,and 13.47,P=0.049,P=0.003,and P<0.01).Conclusion CBATO has a better effect than cTACE and CB in the treatment of rabbits with VX2 liver tumor and can significantly improve tumor necrosis rate,promote the apoptosis of tumor cells,and prolong the survival time of experimental animals.