新型重组融合蛋白MG7-scFv／SEB联合肿瘤坏死因子-α治疗大鼠胃癌移植瘤

Therapeutic effects of MG7-scFv/SEB combined with tumor necrosis factor-alpha on rats xenograft model of human gastric cancer

目的观察新型重组融合蛋白MG7-scFv／SEB联合肿瘤坏死因子-α（TNF-α）对大鼠胃癌移植瘤的治疗作用。方法以人胃癌细胞株SGC-7901建立SD大鼠荷瘤模型，将40只大鼠随机分为4组：即MG7-scFv／SEB组、TNF-α组、MG7-scFv／SEB＋TNF-α组及对照组。连续注射7d后，将大鼠处死，观察各组体内抑瘤效果。结果MG7-scFv／SEB组、TNF-α组及MG7-scF、v／SEB＋TNF-α组肿瘤重量分别为（10．77±0．38）、（9．30±0．39）及（3．86±0．52）g，肿瘤体积分别为（2．18±0．02）、（2．06±0．02）及（1．36±0．02）cm2，均较对照组显著减小（P〈0．01）；MG7-scFv／SEB＋TNF-α组体内抑瘤作用较MG7-、Fv／sEB组、TNF-α组显著增强，差异有统计学意义（P〈0．01）。MG7-scFv／SEB＋TNF-α组肿瘤结节坏死面积显著高于MG7IscFv／sEB组及TNF-α组（＋＋＋比＋＋、＋＋；71．3％比41．2％、43．8％），对照组未见明显肿瘤组织坏死。结论新型重组融合蛋门MG7-scFv／SEB与TNF-α联用对大鼠胃癌移植瘤的体内抑瘤效果明显优于两者单用，MG7-scFv／SEB与TNF-α联合应用町发挥中度协同效应行提高胃癌治疗效果．

Objective To investigate the anti-tumor effect of a novel fusion protein MG7-scFv/ SEB combined with tumor necrosis factor-alpha （TNF-α） on rats xenograft nlodel of human gastric eaneer in vivo. Methods Rat models of human gastric cancer were established by injecting SGC-7901 cells into the right flank of SD rats. Twelve days later, when tumors became palpable, 40 tumor-bearing rats were randomly divided into 4 groups： MG7-scFv/SEB group, TNF-α group, MG7-scFv/SEB ± TNF-α group, and control group. Alter treatment fi）r 7 days consecutively, the rats were sacrificed and the subcutaneous tumors were isolated and measured for observing the anti-tumor effect in vivo. Results The mean tumor weights in MG7-scFv/SEB, TNF-α, and MG7-scFv/SEB ± TNF-α groups were （10. 77 ± 0. 38 ） , （9.30 ± 0. 39） and （3.86 ±0. 52） g, respectively, and the mean tumor volume was （2. 18 ± 0. 02）, （2. 06 ± 0. 02） and （ 1.36 ± 0.02） cru , respectively, which were significantly lighter and smaller than in the eon- trol group （ P 〈 0. 01 for each）. Moreover, in MG7-seFv/SEB ± TNF-αgroup, the growth of gastric tumors was reduced in gastric-tumur-bearing rats as compared to mono therapy groups （P 〈 0. 01 for both）. Immu- nohistoehcmical staining showed that the combined treatment with MG7-scFv/SEB and TNF-α resulted in a massive tumor destruction （ ±±± ; 71.3% ） , compared with a much smaller extent of necrosis following mnno therapy either with MGT-seFv/SEB or TNF-α （ ±± for both; 41.2% or 43.8% , respectively）. In the control tumors, few such changes were observed. Conclusion The anti-tumor effect of MG7-scFv/SEB combined with TNF-α in vivo on rats xenografi model of human gastric： cancer is significantly better than that of mono therapy, which indicates that MG7-scFv/SEB and TNF-α has a moderately synergistic effect on the growth of gastric： tumor in vivo and may be a promising strategy for human cancer therapy.