摘要
目的:建立预测药物敏感性的结直肠癌原代肿瘤模型,并在该模型中进一步评价Ad/Bcl-XL shRNA对结直肠癌的抑制作用。方法:采用结直肠癌手术标本的新鲜组织建立原代肿瘤模型。建模后利用Ad/Bcl-XL shRNA瘤内注射进行后续的抗肿瘤治疗,同时以Ad/GFP和PBS作为对照。治疗后测量肿瘤大小,监测治疗对肿瘤的杀伤作用及正常脏器的毒性作用,并观察裸鼠存活时间。结果:共接种了22例结直肠癌肿瘤标本,有3例标本成瘤,分别命名为NO.9、NO.15和NO.18,它们在形态学上与患者原始肿瘤基本一致。Ad/Bcl-XL shRNA治疗后结果显示,其在3例原代肿瘤模型中均能显著抑制结直肠肿瘤的生长。在NO.9模型中,Ad/Bcl-XL shRNA治疗组的肿瘤体积为(351.4±108.4)mm3,Ad/GFP组和空白对照组则分别为(666±103.6)和(677.3±252.6)mm3,H=8.06,P=0.018;在NO.15模型中,Ad/Bcl-XL shRNA治疗组肿瘤体积为(240.4±83.3)mm3,Ad/GFP组和空白对照组则分别为(474.4±44.4)和(559.9±118.4)mm3,F=19.409,P<0.001;在NO.18模型中,Ad/Bcl-XL shRNA治疗组肿瘤体积为(230.5±187.9)mm3,Ad/GFP组和空白对照组则分别为(619±139.7)和(668.7±246.6)mm3,F=8.966,P=0.003。后续的TUNEL分析显示,Ad/Bcl-XL shRNA诱导肿瘤细胞的凋亡,其凋亡率达到10.98%,明显高于空白对照组的1.52%和Ad/GFP组的1.47%,H=9.38,P=0.009。同时结果还显示,Ad/Bcl-XL shRNA治疗后显著延长了荷瘤裸鼠的存活时间,在模型NO.9中,空白对照组、Ad/GFP组以及Ad/Bcl-XL shRNA组的平均存活时间分别为31、31.4和58d,P=0.009;在模型NO.15中,3组的平均存活时间分别为75.3、84.3和99d,P=0.014;在模型NO.18中,3组的平均存活时间分别为33.4、33.6和72.8d,P=0.046。结论:Ad/Bcl-XL shRNA在结直肠癌原代肿瘤模型中具有明显的抗肿瘤作用,提示其可能是一种潜在的治疗结直肠癌的方法。
OBJECTIVE： To establish a specific colorectal cancer xenografts derived from patient tumors,and further detect the anti-cancer effect of Ad/BcI-XL shRNA on these xenografts. METHODS： Firstly,we established the rectal canc- er xenografts by using the fresh operation specimen of patients with colorectal cancer. Then these xenografts were treated with Ad/Bcl-XL shRNA. Ad/GFP and PBS were used as control groups. After treatment, we monitored the tumor size, detected the apoptosis of tumor tissue and the side effect on normal organs and also recorded the survival time. RESULTS： Three palpable tumors come out from 22 inoculations ,which were named as NO. 9, NO. 15, and NO. 18, respectively. His- tologically,they were similar with the original tumor of corresponding patient. Our results demonstrated that Ad/Bcl-XL shRNA could effectively suppress the tumor growth in all three colorectal cancer xenografts. The tumor volume of Ad/ Bcl-XL shRNA group in model NO. 9 was （351.4±108.4） mm3 ,whereas the tumor volume of Ad/GFP group and PBS group were （666±103.6） and （677.3±252.6） mm3 respectively （H=8.06,P=0. 018）. In model NO. 15,the tumor volume of Ad/Bcl-XL shRNA group was （240.4±83.3） mm3 ,whereas the tumor volume of Ad/GFP group and PBS group were （474.4±44.4） and （559.9±118.4）mm3 ,respectively （F=19. 409,P〈0. 001）. In model NO. 18,the tumor volume of Ad/BcI-XL shRNA group was （230.5±187.9） mm3 , whereas the tumor volume of Ad/GFP group and PBS group were （619 ± 139.7） and （668.7± 246.6） mm3 , respectively （F= 8. 966, P= 0. 003）. Subsequent TUNEL assay indicated that Ad/Bcl-XL shRNA induced obvious apoptosis in tumor tissue,the ratio reached to 10.98% which was significantly higher than that of Ad/ GFP （1.470± ） or PBS group （ 1.52 %）, （ H= 9.38, P = 0. 009）. Our data also showed that Ad/Bcl-XL shRNA prolonged the survival time of nude mice. The over survival of PBS, Ad/GFP and Ad/Bel-XL shRNA groups in model NO. 9 were 31,31.4 and 58 d （P=0. 009）. In Model NO. 15 and NO. 18,they were 75.3,84.3,99 d （P=0. 014） ,and 33.4,33.6,72.8 d （P=0. 046）, respectively. CONCLUSIONS： Our data shows that Ad/Bcl-XL shRNA have effective anti-tumor effects on the colorectal cancer xenografts derived from patient tumor, suggesting it can be a potential way for colorectal cancer treatment.
出处
《中华肿瘤防治杂志》
CAS
北大核心
2014年第9期651-655,共5页
Chinese Journal of Cancer Prevention and Treatment
基金
国家科学自然基金(81272681)
