Adv-mIL-12转染KC治疗人结直肠癌裸鼠移植瘤的实验研究

Treatment of Implanted Lovo Human Colorectal Cancer Cell in Nude Mice By Kupffer Cell Transduced with an Recombinant Adenoviral Vector Expressing Interleukin 12

目的探讨Adv-mIL-12转染KC对人结直肠癌裸鼠移植瘤的抑制作用。方法用人结直肠癌细胞株LoVo建立裸鼠皮下移植瘤模型。五组分别注射NS、Adv-mIL-12、KC、KC-Adv-EGFP及KC-Adv-mIL-12。观察肿瘤生长曲线,脾脏指数(SI),肿瘤组织HE染色,免疫组化检测PCNA、CD34;观察肿瘤细胞增殖情况及微血管密度(MVD)。结果实验组(KC-Adv-mIL-12)瘤体平均体积367.78 mm3,对照组(NS)平均体积676.37 mm3,两者比较差异有统计学意义(P<0.05);实验组SI较对照组增加明显;HE染色提示实验组肿瘤细胞异型性减少、有明显的淋巴细胞浸润。肿瘤组织免疫组化提示:实验组PCNA阳性细胞比率较对照组明显减少(P<0.05),CD34染色标记测定MVD较对照组相比也呈下降趋势。结论 Adv-mIL-12转染KC能有效地抑制裸鼠人结直肠癌移植瘤生长、阻止瘤体微转移,并能提高机体免疫力。

Objective To investigate the effects of Kupffer cells transduced with an recombinant Aden-oviral Vector expressing Interleukin 12 on implanted LoVo human eolorectal cancer Cells in nude mice. Methods Female BALB/C mice（5 each group） were inoculated subcutaneously on their right thighs with 3 × 10^6 LoVo cells. The mice were intratumorally and extratumorally injected with NS,Adv-mIL-12,KC, KC-Adv-EGFPand KC-Adv-mIL-12 respectively. Tumor growth curve was monitored,index of spleen（SI） , HE dyeing about tumor tissue and immunoeytoehemistry was used to detect PCNA and CD34. The proliferation and MVD about different tumor group was recorded. Results The tumor volumes in the mice injected with KC-Adv-mIL-12 were significantly diminished than that with NS, Adv-mIL-12, KC or KC-Adv-EGFP（ KC-Adv-mIL-12 367.78 mm3 ; NS 676.37 mm3 ）, P 〈 0.05. KC-Adv-mIL-12 enhanced significantly the indexes of spleens. The HE dyeing about tumor tissue showed that the heteromorphism about tumour cell was diminished in the the experimental group compared with control groups. The experimental group significantly down-regulated expression of PCNA in tumors infected with KC-Adv-mIL-12 compared with NS （ P 〈 0.05 ） , Adv- mIL-12,KC,KC-Adv-EGFP and there also down-regulated expression of CD34. Conclusion Kupffer cells transduced with Adenoviral Vector expressing Interleukin 12 can inhibit human eoloreetal cancer growth significantly and can enhance organismal immunologic system markedly.