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脂质体-白细胞介素-2基因复合物瘤体内注射治疗肝细胞癌的实验研究 被引量:3

Preliminary studies on the effects of direct gene transfer with liposome-inter- leukin-2 gene complexs into mice hepatocellular carcinoma
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摘要 以阳离子脂质体lipofectin介导含人白细胞介素一2(IL-2)基因的真核表达质粒pME18S-IL-2转染体外培养和体内成瘤的小鼠肝癌HAC细胞,观察IL-2基因转染的肝癌细胞表达IL-2情况及对肝癌的治疗作用。结果:体外转染IL-2基因48小时后在培养上清中可测得人IL-2活性,96小时达最高峰(76U/ml);瘤体内转染后,发现治疗组小鼠生存时间明显延长(32.1±9.4d比20.9±7.5d,P<0.01),肿瘤体积明显小于对照组,瘤组织内可检出IL-2的mRNA。实验表明,脂质体-IL-2基因复合物直接注射人瘤体后可获局部IL-2基因表达,从而诱生机体抗肿瘤效应,这为肝癌基因治疗提供了一种简便实用的模式。 A cationic liposome,lipofectin, was selected as a DNA delivery vector.An eukaryotic expression vector containing human interleukin-2 gene(pME 18S-IL-2)was transduced into hepatocellular carcinoma cell line of mice,HAC,by lipofectin- DNA complexs. The human interleukin-2(IL-2)gene transduced HAC cell began to secrete IL-2 after 48h(30U/ml), reached peak level at 96h(76U/ml) and declined after five days later. Ten days after the complexs introduced directly into subcutaneous nodules of HAC in BALB/C mice,the growth of tumors was significantly delayed as compared with the pME18S group(0.65 ±0.3lcm3vs.1.076 ± 0.43cm3,n=12, P<0.01).The survival period of the treated mice was markedly prolonged as compared with the pME 18S group (32.1±9.4d vs. 20.9 ± 7.5d,n=10, P< 0.01). In the gene transduced tumor nodules, RNA coding for IL-2 was detected by PCR after incubated with reverse transcriptase but not in its absence, suggesting that RNA encoding the gene product was synthesized in vivo. Obvious necrosis in tumor center and infiltration of inflammatorv cells at tumor border were detected bv routine pathological examination. The above results suggest that direct IL-2 gene transfer into hepatocellualr carcinoma can achieve local gene expression and induce the body anti-tumor effect. It might be a practical as well as beneficial therapy of hepatocellular carcinoma.
出处 《中华消化杂志》 CSCD 北大核心 1996年第4期196-199,共4页 Chinese Journal of Digestion
关键词 肝肿瘤 治疗 白细胞介素-2 脂质体 Liver neoplasm/therapy Gene lnterleukin-2 Liposome
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