Tuftsin衍生物TP影响肿瘤相关巨噬细胞 MIP-1α分子表达

摘要

Aim To investigate the effect of TP on the expression of macrophages inflammatory protein ( MIP-1α) . Methods Total RNA of mouse Ana-1 cells and tumor associated macrophages were extracted, and MIP-1α mRNA was detected by RT-PCR. Mouse S180-xenografts were established by injecting S180 cells subcutaneously into the double abdominal flanks of the mice. The postoperative residual tumor models were generated in the right abdominal tumors when tumors grew into 250 mm3 . Animals were treated with TP or CTX, and tumor tissues were separated and MIP-1α was detected by immunohistochemistry. Results There was no significant difference of the expression of MIP-1α between Ana-1 cells and TAMs. TP couldn’ t affect MIP-1αexpression in Ana-1 cells while it signifi-cantly decrease MIP-1α expression in TAMs in a dose-dependent manner. TP significantly decreased MIP-1αexpression of tumor tissue compared with control group. Conclusions MIP-1α will be a new target of TP anti-cancer. Simple cell line tests in vitro couldn’ t reveal the real state in vivo.%目的：探讨TP对肿瘤相关的趋化因子巨噬细胞炎性蛋白1-α( MIP-1α)表达的影响。方法使用RT-PCR的试验方法,检测小鼠巨噬细胞Ana-1细胞和肿瘤组织中提取的巨噬细胞中MIP-1α的表达；建立小鼠S180肉瘤细胞皮下移植瘤双瘤模型,待肿瘤体积生长至约250 mm3时,将其中一侧建立术后残瘤模型,并开始以8 mg·kg-1剂量的TP给药,隔天1次,给药4次后,分离肿瘤组织,免疫组化检测MIP-1α的表达。结果不同浓度TP对小鼠TAMs的MIP-1α表达较空白对照组明显减少,并呈剂量依赖性；体内试验中,TP处理组的荷瘤小鼠的肿瘤组织MIP-1α与对照组相比表达明显降低,接近于阳性药环磷酰胺组；但是 MIP-1α在小鼠Ana-1细胞和TAMs中的 mRNA表达量差异没有统计学意义；不同浓度TP对小鼠Ana-1细胞的MIP-1α表达差异也没有统计学意义。结论 TP 不能影响小鼠 Ana-1细胞系的MIP-1α表达,但TP对肿瘤组织中的巨噬细胞MIP-1α的表达有明显影响；MIP-1α有可能是 TP抗癌作用机制的新靶点。