摘要
目的：研究拉帕替尼与绿原酸联合应用对抑制巨噬细胞M2型极化的影响及其在乳腺癌转移中的作用。方法：采用IL-13建立巨噬细胞M2型极化的体外模型，流式细胞术检测拉帕替尼和绿原酸合用对巨噬细胞M2型表面标志物CD206的影响；实时定量PCR检测拉帕替尼和绿原酸合用对巨噬细胞M2型特异性基因表达的影响；采用自发乳腺癌且发生肺转移的MMTV—PyVT小鼠模型考察两药合用对乳腺癌肺转移的影响，观察肺转移灶组织HE染色结果并统计转移灶点数；免疫荧光法分析乳腺癌组织中巨噬细胞的M2型极化情况。结果：拉帕替尼与绿原酸合用能够有效抑制IL-13诱导的F4／80hiCD206hi细胞（即M2型巨噬细胞）增多[（42．17％±2．59％）与（61．15％±7．58％），P〈0．05]；两药合用能明显下调由IL-13诱导的Yml基因的上调[（1．8±0．0）与（1．0±0．0），P〈0．05]，且其作用比绿原酸单给药组强[（0．9±0．1）与（1．8±0．0），P〈0．051；拉帕替尼与绿原酸合用能显著减少小鼠肺转移灶点数[P〈0．05]；两药合用与对照组比较能降低瘤内CD206阳性细胞所占巨噬细胞的比例I（6．08％±2．60％）与（29．04％±5．86％），P〈0．05]。结论：拉帕替尼与绿原酸的联合用药能有效抑制巨噬细胞的M2型极化以及乳腺癌的转移。
Objective： To determine the effect of the combination of lapatinib with chlorogenic acid on classical macrophage adopted in the study. M2 marker CD206. metastasis of breast cancer in mouse model. Methods： The M2 polarization model induced by interlukinl3 in vitro was Flow cytometric analysis was performed to detect the expression of The transcription of M2-associated genes was measured by RT-PCR. HE staining was used to analyze the metastatic nodes of breast cancer in lungs of MMTV-PyVT mice. Immunostaining analysis was used to detect the expression of related proteins in breast cancer. Results： The combination of lapatinib and chlorogenic acid inhibited the expression of CD206 induced by IL-13 [ （42.17%± 2.59% ） vs （61.15%±7.58% ） , P 〈0.05 ]. The combination more markedly suppressed expression of M2-associated gene Yml than lapatinib alone [ （0.9 ± 0.1 ） vs （ 1.8 ± 0.0）, P 〈 0. 05 ]. The combination of lapatinib and chlorogenic acid significantly reduced metastatic nodes in lung [ P 〈 0.05 ], and also significantly decreased the percentage of CD206 ＋ cells in breast cancer compared to controls [ （6.08% ± 2.60% ） vs （ 29.04%± 5.86% ）, P 〈 0.05 ]. Conclusion： The combination of lapatinib and chlorogenic acid can effectively inhibit macrophage M2 polarization and metastasis of breast cancer.
出处
《浙江大学学报（医学版）》
CAS
CSCD
北大核心
2015年第5期493-499,共7页
Journal of Zhejiang University(Medical Sciences)
基金
浙江省自然科学基金(LY14H310008)
浙江省教育厅科研项目(Y201226213)
