| 丁志江,乔 涵,赵晓燕,等.白藜芦醇调控巨噬细胞极化状态对鼻咽癌转移能力的影响及其机制[J].肿瘤学杂志,2026,32(10):876-885. |
| 白藜芦醇调控巨噬细胞极化状态对鼻咽癌转移能力的影响及其机制 |
| The Effect of Resveratrol Regulating Macrophage Polarization Status on the Metastatic Ability of Nasopharyngeal Carcinoma and Its Mechanism |
| 投稿时间：2026-04-20 |
| DOI：10.11735/j.issn.1671-170X.2026.10.B009 |
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| 中文关键词: 白藜芦醇 鼻咽肿瘤 巨噬细胞 转移 信号通路 |
| 英文关键词:resveratrol nasopharyngeal neoplasms macrophage metastasis signaling pathway |
| 基金项目:云南省教育厅科学研究基金项目（2025J0318） |
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| 中文摘要: |
| 摘 要：［目的］ 探讨白藜芦醇（resveratrol，RES）调控肿瘤相关巨噬细胞的极化状态对鼻咽癌（nasopharyngeal carcinoma，NPC）转移能力的影响，并探讨其分子机制。［方法］（1）诱导M2型巨噬细胞：佛波酯（PMA）体外诱导人白血病单核细胞THP-1形成M0巨噬细胞，流式细胞术检测标志CD11B的M0巨噬细胞；NPC CNE2细胞与M0巨噬细胞共培养诱导M2型巨噬细胞，流式细胞术检测标志CD163、CD206的M2型巨噬细胞，实时荧光定量PCR（quantitative real-time PCR，qPCR）检测细胞因子IL-10、TGF-β1的表达水平。（2）RES对巨噬细胞极化状态的影响：40 μmol/ LRES处理M2型巨噬细胞24 h：流式细胞术检测表达CD163、CD206的M2型巨噬细胞以及表达CD80、CD86的M1型巨噬细胞的占比，qPCR检测CD163、TGF-β1、IL-10的变化；Western blot实验检测PI3K、p-AKT蛋白的表达水平。（3）RES通过调控巨噬细胞对NPC转移能力的影响：分别以M2型巨噬细胞上清液培养基（M2-CM）、经RES处理24 h后的M2型巨噬细胞上清液培养基（RES-M2-CM）培养NPC细胞24 h，Transwell实验检测两组细胞的迁移、侵袭能力，Western blot实验检测两组细胞中MMP-2、MMP-9、E-cadherin、Vimentin蛋白的表达水平。［结果］（1）成功诱导M2型巨噬细胞：PMA诱导THP-1细胞过程中，光学显微镜下观察到细胞形态发生变化，流式细胞术检测发现表达 CD11B的M0巨噬细胞增多；M0巨噬细胞经CNE2-CM共培养24 h后，流式细胞术检测发现表达CD163、CD206的M2型巨噬细胞数目增多，qPCR检测提示CD163、TGF-β1、IL-10表达升高。（2）RES处理M2型巨噬细胞24 h后：流式细胞术检测发现表达CD163、CD206的巨噬细胞减少（P＜0.001），表达CD80、CD86的巨噬细胞增多（P＜0.01）；qPCR检测发现CD163、 TGF-β1、IL-10表达水平降低（P＜0.01）；Western blot实验发现PI3K、p-AKT蛋白表达水平下降（P＜0.05）。（3）Transwell实验发现与M2-CM共培养的NPC细胞的侵袭、迁移能力增强，与RES-M2-CM共培养的NPC细胞的侵袭、迁移能力减弱（P＜0.001）；Western blot实验发现，与M2-CM共培养的NPC细胞的E-cadherin蛋白表达水平降低，Vimentin、MMP-2、MMP-9蛋白表达水平升高（P＜0.05），与RES-M2-CM共培养的NPC细胞的E-cadherin蛋白表达水平增高，Vimentin、MMP-2、MMP-9蛋白的表达水平降低（P＜0.05）。［结论］ RES可通过PI3K/AKT信号通路将M2型巨噬细胞逆转成M1型巨噬细胞；RES可通过调控巨噬细胞的极化状态上调E-cadherin、下调Vimentin的表达水平，抑制上皮间质转化，进而降低NPC的迁移能力，并可通过下调MMP-2、MMP-9的表达水平抑制NPC的侵袭能力。 |
| 英文摘要: |
| Abstract： ［Objective］ To investigate the effect of resveratrol (RES) on the polarization state of tumor-associated macrophage and its impact on the metastatic ability of nasopharyngeal carcinoma (NPC)， and to explore its molecular mechanisms.［Methods］ (1) Induction of M2-type macrophages： phorbol 12-myristate 13-ace-tate (PMA) was used to induce M0 macrophages from human leukemia monocytes THP-1， flow cytometry (FCM) was employed to detect M0 macrophages marked by CD11B； NPC CNE2 cells were co-cultured with M0 macrophages， FCM was used to detect M2-type macrophages marked by CD163 and CD206， and quantitative real-time PCR (qPCR) was used to detect IL-10 and TGF-β1. (2) Effects of RES on the polarization state of macrophages： M2-type macrophages were treated with 40 μmol/L RES for 24 h， FCM was used to detect the proportion of M2-type macrophages expressing CD163 and CD206， as well as M1-type macrophages expressing CD80 and CD86； qPCR was used to detect the changes in CD163， TGF-β1， and IL-10；Western blot was used to detect the expression levels of PI3K and p-AKT proteins. (3) Effects of RES on the metastasis ability of NPC cells by regulating macrophages： NPC cells were cultured for 24 h in M2-CM and RES-M2-CM respectively， Transwell assay was used to detect the migration and invasion abilities， Western Blot was used to detect the expression levels of MMP-2， MMP-9， E-cadherin， Vimentin proteins in the two groups of cells. ［Results］ (1) Successful induction of M2-type macrophages： during the process of PMA-induced THP-1 cell transformation， changes in cell morphology were observed under an optical microscope， and FCM detection revealed an increase in cells expressing CD11B； after 24 h of co-culture with CNE2-CM， FCM detection found an increase in the number of M2-type macrophages expressing CD163 and CD206， and qPCR detection suggested elevated expression of CD163， TGF-β1， and IL-10 cytokines. (2) After RES treatment of M2-type macrophages for 24 h， the number of macrophages expressing CD163 and CD206 decreased(P＜0.001)， while the number of macrophages expressing CD80 and CD86 increased (P＜0.01)； the expression levels of CD163， TGF-β1， and IL-10 decreased(P＜0.01)， Western blot experiments revealed a decrease in the expression levels of PI3K and p-AKT proteins(P＜0.05). (3) The Transwell experiment revealed that the invasive and migratory abilities of NPC cells were enhanced in witch co-cultured with M2-CM but were weakened in witch co-cultured with RES-M2-CM(P＜0.001). The Western Blot experiment showed that the expression of E-cadherin in NPC cells decreased in witch co-cultured with M2-CM but increased in witch co-cultured with RES-M2-CM； the expression levels of Vimentin， MMP-2， and MMP-9 increased in witch co-cultured with M2-CM but decreased in witch co-cultured with RES-M2-CM(P＜0.05).［Conclusion］ RES can reverse M2-type macrophages into M1-type macrophages through the PI3K/AKT signaling pathway； RES can suppress the migration of nasopharyngeal carcinoma by inhibiting EMT via increasing the expression level of E-cadherin and decreasing the expression level of Vimentin， it can also inhibit the invasion ability of NPC by down-regulating the expression levels of MMP-2 and MMP-9. |
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