摘要
目的研究碘-131标记的重组人肿瘤坏死因子-α(rhTNF-α)在荷人肝癌裸鼠的治疗应用。方法通过131I-rhTNF-α和人肝癌SMMC-7721细胞的体外结合以检测131I-rhTNF-α的生物学活性;采用单细胞悬液接种法,制备荷人肝癌裸鼠模型;在一定的时间(30min、1h、6h、12h、24h、48h)将相同数量的荷人肝癌裸鼠分批处死,研究131I-rhTNF-α在荷人肝癌裸鼠体内的分布,获得131I-rhTNF-α在荷人肝癌裸鼠的主要浓聚组织及在肿瘤组织的浓聚特点;通过大体观察、活组织病理检查等考察131I-rhTNF-α对荷人肝癌裸鼠肿瘤生长的影响。结果131I-rhTNF-α与SMMC-7721细胞体外结合实验得出,131I-rhTNF-α有很好的生物学活性,与SMMC-7721细胞的结合存在饱和,在一定范围内呈剂量依赖。131I-rhTNF-α在肿瘤组织的浓聚特点为,肿瘤组织可以浓聚较多的131I-rhTNF-α,且储留时间较长;给药后6h肿瘤组织的放射性达到高峰,48h仍旧保留有高峰时放射性的67.5%。与阴性对照组(生理盐水组)相比,静脉或瘤内注射131I-rhTNF-α2次(每次注射量相当于50kg人体注射41.58GBq,间隔为14d)均有较强的肿瘤抑制作用,抑瘤率分别为68.9%和72.5%,二者的抑瘤作用与阳性对照组(阿霉素组)比较差异无统计学意义(P>0.05),与131I(9.2%)、rhTNF-α(20.3%)和阴性对照组比较差异有统计学意义(P<0.05)。结论131I-rhTNF-α在荷人肝癌裸鼠体内能有效抑制肿瘤生长。
Objective To test the effect of recombinant human tumor necrosis factor-α（rhTNF-α） labeled with ^131 I on tumor growth in the nude mice bearing human hepatoma. Methods The biological activity of ^131I rhTNF-α was tested through in vitro combination of the radioactive drug and SMMC-7721 cells. The BALB/c-nu/ nu mice model bearing human hepatoma were established by injecting single cell suspension of SMMC-7721 cells. When the tumor was 1 cm in diameter, the therapeutic experiment was carried out. Twenty-four nude mice bearing human hepatoma were divided into six groups according the area of tumor, weight and sex of the nude mice. After i. v administration of ^131 I-rhTNF-α, the body biodistribution of ^131 I-rhTNF-α was assessed during a short-term （30 min,1 h,6 h） and a long-term （12 h, 24 h, 48 h） period. The biological activity and tumor accumulation of ^131I- rhTNF-α were investigated. In the end of the experiment, histopathologic examinations of tumor samples were undertaken. Results The combination of ^131I rhTNF-α with the human hepatoma SMMC-7721 cells existed dose dependence and saturability. The 131 I-rhTNF-α had satisfactory immunoreactivity. The ^131 I-rhTNF-α accumulated in tumor tissues well and kept stable for several days. The tumor tissues accumulated the highest radioactivity at 6 h, and still maintained 67. 5% of that radioactivity at 48 h. The ^131 I-rhTNF-α administrated either intravenously or intratumorally could inhibit tumor growth. The ^131I-rhTNF-α had similar radioactivity as the positive control （P〉0.05）, but greater radioactivity than the control groups including ^131 I, rhTNF-α and the negative groups （P〈0.05）. Conclusion The radioactive compound of ^131 I-rhTNF-α can inhibit and kill tumor cells, which demonstrates its potential for treating hepatocarcinoma.
出处
《四川大学学报（医学版）》
CAS
CSCD
北大核心
2009年第5期787-792,共6页
Journal of Sichuan University(Medical Sciences)
基金
国家自然科学基金(批准号30370424)资助
