益气除痰方抑制肿瘤相关巨噬细胞的抗肿瘤免疫功能研究

Effect of Yiqi Chutan Formula on anti-tumor immunity response through inhibiting production of tumor-associated macrophages

目的周岱翰教授的经验方益气除痰方(Yiqi Chutan Formula,YQCTF)具有"培土生金"的作用,已通过临床试验证明对非小细胞肺癌(non-small cell lung cancer,NSCLC)具有较好的疗效,但是其精确抗肿瘤分子机制有待进一步阐明。本研究探讨YQCTF对肿瘤微环境中肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)的影响。方法构建Lewis肺癌(Lewis lung carcinoma,LLC)的小鼠移植瘤模型,以检测YQCTF对小鼠体内移植瘤的影响;同时,应用流式细胞分选技术,以CD11b-PE和F4/80-FITC标记抗体测定移植瘤中TAMs,测定YQCTF对小鼠肺癌移植瘤中TAMs产生的影响。结果与对照组相比,YQCTF能较强地抑制小鼠体内移植瘤的生长。2.5g/kg YQCTF处理组的抑瘤率达51.37%,5.0g/kg YQCTF处理组的抑瘤率达68.46%。并且,YQCTF能较强地抑制小鼠移植瘤中TAMs的产生,相比较于溶剂对照组的CD11b+F4/80+TAMs占所有CD11b+细胞比例为(21.81±2.66)%,2.5g/kg YQCTF处理组的CD11b+F4/80+TAMs占所有CD11b+细胞群比例为(11.47±1.64)%,5.0g/kg YQCTF处理组的CD11b+F4/80+TAMs占所有CD11b+细胞群比例为(6.53±1.57)%,且YQCTF处理组均与溶剂对照组比较差异有统计学意义,均P<0.05。结论 YQCTF可抑制肿瘤微环境中TAMs的产生,从而达到抗肿瘤免疫的效应。

OBJECTIVE Yiqi Chutan Formula （YQCTF） is a principle and effective prescription designed by Daihan Zhou, to treat lung cancer in the Department of Oncology of the First Affiliated Hospital of Guangzhou Traditional Chi- nese Medicine University. However, the antitumour effect and mechanisms of YQCTF remain incompletely understood and characterized. This study explored the function of YQCTF on tumor-associated macrophages （TAMs） by using this primary homograft model （Lewis lung carcinoma, LLC）. METHODS The in vivo anti-tumor efficacy of YQCTF was ex- amined in the LLC tumor bearing C57BL/6 mice homograft model. In addition, the effect of YQCTF on the production of TAMs in the tumor tissue with or without YQCTF treatment was determined by flow cytometry analysis after stained with CDllb-PE and F4/80-FITC antibody. RESULTS YQCTF could suppressed the growth of lung cancer xenografts, and we observed up to 51.37% decrease of the tumor growth rate in the 2.5 g/kg YQCTF group and correspondingly 68.46% decrease in the 5.0 g/kg YQCTF group. Meanwhile, in subcutaneous homograft models of lung carcinoma, YQCTF protein could strongly inhibit the production of TAMs, which we found that YQCTF-induced TAMs levels with CD11b^＋ F4/80^＋ in isolated tumors were significantly lower in 2.5 g/kg group （11.47± 1.64）% and 5.0 g/kg group （6.53±1.57）% than that in control group （21.81±2.66）% （all P〈0.05）. CONCLUSIONS YQCTF can inhibite the production of TAMs, and promote the anti-tumor immunity response.