内皮抑素-血管内皮细胞抑制因子重组腺病毒对荷胃癌裸鼠的治疗

Therapeutic effect of endostatin-vascular endothelial growth inhibitor recombinant adenoviruses on gastric carcinoma in nude mice

目的:研究重组腺病毒携带hENDO-VEGI_(151)融合基因治疗胃癌的可行性。方法:分别用 500 μL滴度为 1×10^(12)TCID_(50)/L的粗制重组腺病毒AdCA13—hENDO—VEGI_(151)或AdLacZ皮下注射治疗荷胃癌裸鼠,隔天1次,共注射10次。最后一次注射24h后处死动物,检测肿瘤体积、抑瘤率、目的基因的表达、增生细胞核抗原指数(PCNA LI)、肿瘤细胞凋亡指数(AI)、肿瘤微血管密度(MVD)。结果:注射AdCA13-hENDO-VEGI_(151)的治疗组肿瘤体积为328±156mm^3,注射AdLacZ的对照组肿瘤体积为2356±1 140 mm^3,差异显著(F=12.42,P=0.0125),抑瘤率为86.1％;重组腺病毒携带的目的基因均能在荷胃癌裸鼠肿瘤组织中表达;治疗组PCNA LI为 0.13± 0.09％,对照组为 1.40 ± 0.53％,差异显著(F=22.30,P=0.0033);治疗组AI为5.09 ± 0.25％,对照组AI为0.61±0.67％,差异显著(F=155.13,P=0.0 001);治疗组MVD为0.06±0.03％,对照组MVD为 1.09 ± 0.76％,差异明显(F=7.38,P=0.0348)。结论:重组腺病毒携带的融合基因能在荷胃癌裸鼠体内表达出有生物学活性的融合蛋白,并表现出一定的抑瘤效果。

AIM: To investigate the effects of recombinant adenoviruses carrying the endostatin-VEGI_(151) fusion gene AIerapy on gastric carcinoma in nude mice. METHODS: Human gastric carcinoma SGC7901 cells (5x10^6) were injected sc into the dorsal midline of nude mice (3 weeks old), and 500 μL (10^(12) TCID_(50)/L) of recombinant adenoviruses AdCA13-hENDO-VEGI_(151) or AdLacZ was given respectively sc every other day for ten times. Twenty-four hours after the last injection, tumor size, inhibition rate, expression of target gene, proliferating cell nuclear antigen label index (PCNA LI). apoptotic index (AI), and intratumoral microvessel density (MVD) were evaluated respectively after the mice were sacrificed. RESULTS: Compared with the control group AdtacZ (2 356± 1 140mm^3), the average tumor size of group AdCA13- hENDO-VEGI_(151) was reduced in size(328±156 mm^3,F=12.42, P=0.0125) with an inhibition rate of 86.1 %. The adenoviruses carriyring the target gene could be expressed in gastric carcinoma. The PCNA LI of the treated mice (0.13±0.09 %) was lower than the contol (1.40±0.53 %, F=22.30, P=0.0033), The AI was higher in the treated mice (5.09±0.25 %),than in the control (0.61±0.67 %, F=155.13, P=0.0001).The MVD was lower in the treated mice (0.06±0.03 %) than in the control (1.09±0.76 %, F=7.38, P=0.0348). CONCLUSION: The recombinant adenovirus carrying fusion gene of hENDO-VEGI_(151) can express the fuion protein in gastric carcinoma in nude mice and inhibit the tumor growth,