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目的探讨联合三氧化二砷(As2O3)与B7-H3基因治疗肿瘤的协同效应。方法分别建立小鼠肝癌的大肿瘤和多发肿瘤模型,序贯法瘤内注射真核表达质粒pcDNA3.1-Flag-B7-H3和As2O3,监测大肿瘤及多发性肿瘤的生长情况;免疫组织化学和免疫印记(Westernblot)检测B7-H3基因的表达;CD31免疫组织化学染色评估抗肿瘤血管化的效果;TUNEL检测肿瘤细胞的凋亡情况。结果单用B7-H3基因或As2O3治疗大肿瘤只能使肿瘤暂时缩小而不能消退;联合治疗不但可以治愈大肿瘤,而且可以根除多发性肿瘤。免疫组织化学及Westernblot检测结果表明B7-H3基因在肿瘤细胞内表达。联合治疗使肿瘤组织的微血管密度显著减少(P<0.01),肿瘤细胞的凋亡显著增加(P<0.01)。结论联合治疗可以有效地根治大肿瘤和多发性肿瘤。
Objective To investigate the synergistic effect of combining arsenic trioxide (As2O3) and B7-H3 gene therapy on tumors. Methods The large and multiple tumor models of mouse hepatocellular carcinoma were established respectively. The eukaryotic expression plasmids pcDNA3.1-Flag-B7-H3 and As2O3 were injected intratumorally in order to monitor the growth of large and multiple tumors. Immunohistochemistry And Western blot were used to detect the expression of B7-H3 gene. The anti-tumor vascularization effect was evaluated by CD31 immunohistochemical staining. The apoptosis of tumor cells was detected by TUNEL. Results Treatment of large tumors with B7-H3 gene alone or As2O3 could only temporarily reduce the tumor size but not disappear. Combination therapy can not only cure large tumors but also eradicate multiple tumors. Immunohistochemistry and Western blot results showed that B7-H3 gene was expressed in tumor cells. The combination therapy reduced the microvessel density (P <0.01) and the apoptosis of tumor cells significantly (P <0.01). Conclusion Combined treatment can effectively cure large tumors and multiple tumors.