LPS诱导巨噬细胞M1型极化对肿瘤生长的影响

目的 研究脂多糖（lipopolysaccharide，LPS）诱导巨噬细胞M1型极化对肿瘤生长的影响。方法 将Balb/c雌性小鼠随机分为对照组和实验组。Renca细胞皮下建模，待肿瘤体积生长至50mm3时瘤旁注射生理盐水（100μl/只， 1次/2d）或LPS（100μg/只，1次/2d），采用流式细胞术检测肿瘤相关巨噬细胞M1型极化水平。将小鼠肿瘤细胞系（ML-1、MC38、Renca）分成三组：空白组（完全培养基加入50%DMEM基础培养基）、对照组（完全培养基加入50%巨噬细胞培养基上清液）和实验组（完全培养基加入50%LPS预处理的巨噬细胞培养基上清液）。采用细胞计数试剂-8（cell counting kit-8，CCK-8）实验检测肿瘤细胞增殖情况；采用流式细胞术检测肿瘤细胞周期及凋亡情况。 结果 经LPS处理后肿瘤相关巨噬细胞M1型比例增多（P<0.001），从而增强其抗肿瘤功能；LPS诱导巨噬细胞M1型极化可显著抑制肿瘤细胞的增殖（Renca：P=0.023；ML-1：P=0.045）；LPS诱导巨噬细胞M1型极化可引起肿瘤细胞周期G0/G1（MC38：P=0.011；ML-1：P=0.022）或S期（Renca：P=0.022）阻滞，进而抑制细胞分裂；LPS诱导巨噬细胞M1型极化可引起肿瘤细胞凋亡（Renca：P=0.04；ML-1：P=0.007）。结论 LPS可通过诱导巨噬细胞M1型极化发挥抗肿瘤功能。

Effect of LPS-induced M1 polarization of macrophages on tumor growth

Objective To study the effect of lipopolysaccharide (LPS)-induced M1 polarization of macrophages on tumor growth. Methods Female Balb/c mice were randomly divided into control group and experimental group. Renca cells were used to establish subcutaneous tumor model. NaCl (100μl/mice, once every two days) or LPS (100μg/mice, once every two days) was injected to the tumor side when the tumor grew to 50mm3. The M1 polarization level of tumor-associated macrophages was detected by flow cytometry. Mouse tumor cell lines (ML-1, MC38, Renca) were divided into three groups: blank group (complete medium with 50% DMEM basal medium), control group (complete medium with 50% medium supernatant of cultured macrophages) and experimental group (complete medium with 50% medium supernatant of LPS pretreated cultured macrophages). The proliferation of tumor cells was detected by cell counting kit-8 (CCK-8). The cell cycle and apoptosis of tumor cells were detected by flow cytometry. Results The proportion of tumor-associated macrophages M1 increased after LPS treatment (P<0.001), thus enhancing its anti-tumor function. LPS-induced M1 polarization of macrophages can significantly inhibit the proliferation of tumor cells (Renca: P=0.023, ML-1: P=0.045). LPS-induced M1 polarization of macrophages blocked G0/G1 phase (MC38: P=0.011, ML-1: P=0.022) or S phase (Renca: P=0.022) of tumor cell cycle, and then cell division was inhibited. LPS-induced M1 polarization of macrophages significantly induced apoptosis of tumor cells (Renca: P=0.04, ML-1: P=0.007). Conclusion LPS can play an anti-tumor role by inducing M1 polarization of macrophages.