B7-H3基因与三氧化二砷联合治疗肿瘤的协同效应

B7-H3 mediated gene therapy synergizes with arsenic trioxide to combat solid tumors

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 synergism of B7-H3 gene therapy and arsenic trioxide in the treatment of solid tumors.Methods Tumors were subcutaneously established in mice,and received injection with PVP complex containing B7-H3 expression plasmid,or As_2O_3,or both of them.The growth of tumors was monitored.Expression of B7-H3 was detected by immunohistochemistry and Western blotting.The vascular status of tumors was also evaluated.Results Gene transfer of expression plasmid encoding B7-H3 induced the rejection of small established tumors;but it could only retard the growth of large tumors.Whereas combinational therapy with As_2O_3 and B7-H3 eradicated large tumors.Combined therapy enhanced apoptosis of tumor cells and reduced the density of tumor blood vessels.Conclusion As_2O_3 reduces vessel density,and enhances B7-H3-mediated immunotherapy.Strategies targeting B7-H3 gene immunotherapy and As_2O_3 have therapeutic potential in treating cancers.