瘤体内注射肿瘤坏死因子重组腺病毒对大鼠乳腺癌的治疗作用

目的:观察腺病毒重组肿瘤坏死因子(TNF)基因转染对大鼠乳腺癌细胞Walker256体内致瘤性的影响及瘤体内注射TNF重组腺病毒对Walker256荷瘤大鼠的治疗作用.方法:Walker256乳癌细胞感染人TNF重组腺病毒后,观察其体外增殖能力、皮下致瘤性的变化及进行肿瘤局部病理学检查;瘤体局部注射TNF重组腺病毒(Ad.hTNF),观察荷瘤大鼠的肿瘤生长情况及生存期.结果:Walker256感染人TNF重组腺病毒后,培养上清中24 h TNF的分泌量达5.2 ng/106细胞,细胞形态学无明显变化,体外增殖能力和皮下致瘤性显著下降,瘤体周围有大量淋巴细胞及单核细胞浸润;肿瘤局部注射Ad.hTNF能显著抑制Walker256的生长,并延长荷瘤大鼠的生存期.结论:重组腺病毒能有效介导TNF基因转染Walker256细胞,瘤体内局部注射Ad.hTNF对Walker256荷瘤大鼠具有明显的治疗作用.

Therapeutic effects of intratumoral administration of TNF recombinant adenoviruses on breast carcinoma in rats

Objective: To investigate the effects of TNF gene transduction on biological characteristics of rat breast carcinoma Walker256 cells and the therapeutic effects of intratumoral injection of TNF recombinant adenoviruses on Walker256 tumor-bearing rats. Methods: Walker256 cells were infected with human TNF recombinant adenoviruses in vitro, and their proliferation in vitro and tumorigenicity were studied; Walker256 tumor-bearing rats were administered with TNF adenoviruses intratumorally, and the tumor growth and animal survival were monitored. Results: After infected with TNF recombinant adenoviruses in vitro, Walker256 cells secreted human TNF at the levels of 5.2 ng/10 6 cells every 24 h, with decreased in vitro proliferation capacity but without obvious morphological changes. The tumorigenicity of TNF gene-transfected Walker256 cells decreased markedly with amounts of lymphocytes and monocytes infiltrating in tumor tissues. Intratumoral injection of TNF recombinant adenoviruses significantly inhibited tumor growth and eventually resulted in tumor regression. Conclusion: Intratumoral administration of TNF recombinant adenoviruses is an effective approach to cancer immunotherapy in Walker256 tumor model.