目的 利用荷瘤小鼠模型探讨香菇多糖联合干扰素调节因子3（IRF3）表达腺病毒载体治疗肿瘤的价值及潜在的机制。方法 利用荷瘤Balb/c小鼠，分别接种磷酸盐缓冲液（PBS）、空白对照腺病毒载体（AdGFP）、香菇多糖、表达活化型IRF3的腺病毒载体（AdIRF3）及香菇多糖联合AdIRF3，观察荷瘤小鼠的肿瘤生长曲线；利用Real-time PCR检测肿瘤组织的β干扰素（IFN-β）水平，酶联免疫斑点检测法（ELISPOT）检测脾脏淋巴细胞功能，流式细胞术（FACS）检测肿瘤局部淋巴细胞比例；记录荷瘤Balb/c裸鼠的肿瘤生长曲线，以及α干扰素受体1（IFNAR1）抗体封闭Balb/c的IFNAR后肿瘤生长曲线。结果 与对照组相比，香菇多糖联合AdIRF3可抑制Balb/c荷瘤小鼠肿瘤生长，且肿瘤局部组织中IFN-β显著高于对照组；肿瘤组织浸润CD8⁺T细胞比例显著高于对照组，而调节性T细胞（Treg）细胞比例在各组间并无显著性差异；ELISPOT显示联合处理刺激淋巴细胞分泌γ干扰素（IFN-γ）的能力显著高于对照组；荷瘤Balb/c裸鼠在接受不同组处理后，各组间的肿瘤生长曲线并无显著差异；利用IFNAR1封闭抗体阻断干扰素作用后，荷瘤Balb/c小鼠再次接受不同组处理，结果显示封闭抗体处理后可抑制香菇多糖联合AdIRF3的肿瘤抑制作用。结论 香菇多糖联合AdIRF3通过活化IRF3-IFN通路发挥协同抑制乳腺癌肿瘤生长的作用。

Objective To investigate the effect of lentinan (LNT) combined with IRF3 expressing adenovirus vector on the anti-tumor therapy, and its underlying mechanism. Methods Balb/c bearing TUBO mice were treated with PBS, AdGFP, AdIRF3, LNT, and LNT combined with AdIRF3 to observe the tumor growth curve of mice. qPCR was used to detect the IFN-β level of tumor tissues. ELISPOT was to check the IFN-γ secretion of spleen cells. FACS was used to make sure the percentage of tumor infiltrated T cells. Balb/c-nu mice were inoculated with TUBO cells, and tumor growth was monitored. Anti-IFNAR1 antibody was injected to Babl/c bearing mice, and tumor growth was measured. Results Compared with control groups, LNT combined with AdIRF3 can inhibit the tumor growth and increase the IFN-γ secretion of TUBO-bearing mice. There was no significant difference of the percentage of tumor infiltrated Treg among groups, but the tumor infiltrated CD8⁺T was significantly higher in LNT combined with AdIRF3 treated mice group. There was no significant difference of tumor growth between Balb-nu mice inoculated with TUBO cells treated by LNT/AdIRF3 and PBS/AdGFP group. The tumor growth was not inhibited in Babl/c bearing mice injected with anti-IFNAR1 antibody and treated by LNT/AdIRF3. Conclusion LNT combined with AdIRF3 can inhibit the tumor growth by activating the IRF3-IFN signaling pathway.

国家自然科学基金资助项目“基于IRF3/IFN通路探讨香菇多糖联合IRF3腺病毒载体的抗乳腺癌作用及机制研究”（81503392）