Our previous research demonstrated that the Wenxia Changfu Formula(WCF),as a neoadjuvant therapy,inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis.Given tumor-associ...Our previous research demonstrated that the Wenxia Changfu Formula(WCF),as a neoadjuvant therapy,inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis.Given tumor-associated macrophages(TAMs)in epithelial-mesenchymal transition(EMT),this study investigated whether WCF impedes lung cancer metastasis by attenuating TAM-induced EMT in non-small cell lung cancer(NSCLC)cells.Utilizing a co-culture model treated with or without WCF,we observed that WCF downregulated cluster of differentiation 163(CD163)expression in macrophages,reduced CCL18 levels in the conditioned medium,and inhibited the growth,invasion,and EMT of NSCLC cells induced by macrophage co-culture.Manipulation of CCL18 levels and Src overexpression in NSCLC cells revealed that WCF’s effects are mediated through CCL18 and Src signaling.In vivo,WCF inhibited recombinant CCL18(rCCL18)-induced tumor metastasis in nude mice by blocking Src signaling.These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-induced EMT via antagonistic modulation of CCL18,providing evidence for its potential development and clinical application in NSCLC patients.展开更多
Objective:To study the effect of inhalant combined with Dingchuan Zhike decoction therapy on the airway remodeling, inflammation and PARC/CCL-18 pathways in patients with cough variant asthma.Methods: A total of 60 pa...Objective:To study the effect of inhalant combined with Dingchuan Zhike decoction therapy on the airway remodeling, inflammation and PARC/CCL-18 pathways in patients with cough variant asthma.Methods: A total of 60 patients with cough variant asthma who were treated in our hospital between January 2014 and May 2016 were collected and divided into the control group (n=30) who received conventional inhalant treatment and the observation group (n=30) who received inhalant combined with Dingchuan Zhike decoction treatment according to single-blind randomized controlled method, and the treatment lasted for 6 months. Before treatment and after 6 months of treatment, high-resolution CT was used to determine the airway remodeling index levels, RIA method was used to detect the peripheral blood airway remodeling index contents, and enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of inflammatory mediators in induced sputum and the PARC/CCL-18 in serum.Results: Before treatment, the differences in the airway remodeling degree as well as the contents of inflammatory mediators and PARC/CCL-18 were not statistically significant between the two groups. After 6 months of treatment, CT airway remodeling indexes LA and TA levels of observation group were higher than those of control group while WA level was lower than that of control group, and peripheral blood airway remodeling indexes CTGF, YKL-39, MMP-9 and TIMP-1 contents were lower tha=n those of control group;inflammatory mediators IL-5, IL-6 and IL-8 contents in induced sputum of observation group were lower than those of control group, and serum PARC/CCL-18 content was lower than that of control group.Conclusion:Inhalant combined with Dingchuan Zhike decoction can inhibit the airway remodeling and reduce the airway inflammation in patients with cough variant asthma.展开更多
目的探讨CCL18-PITPNM3(CC chemokine ligand 18-phosphatidylinositol transfer protein 3,CCL18-PITPNM3)配体受体轴在头颈鳞状细胞癌侵袭转移中的作用及其分子机制。方法采用人重组蛋白CCL18处理头颈鳞状细胞癌Tu686、6-10B细胞,siRN...目的探讨CCL18-PITPNM3(CC chemokine ligand 18-phosphatidylinositol transfer protein 3,CCL18-PITPNM3)配体受体轴在头颈鳞状细胞癌侵袭转移中的作用及其分子机制。方法采用人重组蛋白CCL18处理头颈鳞状细胞癌Tu686、6-10B细胞,siRNA下调PITPNM3的表达,通过CCK-8(cell counting kit-8)、平板克隆实验、流式周期检测生长增殖能力的变化,划痕愈合实验、Transwell侵袭小室实验检测体外迁移侵袭能力的改变,qRT-PCR、Western blot检测EMT分子标志物的表达情况。结果①rhCCL18处理头颈鳞状细胞癌Tu686、6-10B细胞后,细胞划痕愈合率增加,穿过Transwell聚碳酸酯膜的细胞明显增多,rhCCL18处理siRNA下调PITPNM3的Tu686、6-10B细胞,下调组细胞的迁移和侵袭能力较亲本细胞处理组明显减弱;②rhCCL18处理头颈鳞状细胞癌Tu686、6-10B细胞,mRNA水平E-cadherin表达降低,Vimentin、N-cadherin、Fibronectin表达升高;蛋白质水平E-cadherin表达降低,Vimentin表达升高。下调两株细胞的PITPNM3表达后rhCCL18再次处理,E-cadherin下调和Vimentin、N-cadherin、Fibronectin上调均未显示出亲本细胞的明显趋势;③rhCCL18处理和下调PITPNM3对Tu686、6-10B 6组细胞的生存率、增殖及细胞周期无明显变化。结论CCL18-PITPNM3配体受体轴可促进头颈鳞状细胞癌的体外侵袭转移能力,可能与EMT转化相关。展开更多
基金supported by the National Natural Science Foundation of China(No.82274406,81774198)Zhejiang Provincial Natural Science Foundation of China(No.LZ24H270001)the Postgraduate Scientific Research Fund of Zhejiang Chinese Medical University(No.2022YKJ14).
文摘Our previous research demonstrated that the Wenxia Changfu Formula(WCF),as a neoadjuvant therapy,inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis.Given tumor-associated macrophages(TAMs)in epithelial-mesenchymal transition(EMT),this study investigated whether WCF impedes lung cancer metastasis by attenuating TAM-induced EMT in non-small cell lung cancer(NSCLC)cells.Utilizing a co-culture model treated with or without WCF,we observed that WCF downregulated cluster of differentiation 163(CD163)expression in macrophages,reduced CCL18 levels in the conditioned medium,and inhibited the growth,invasion,and EMT of NSCLC cells induced by macrophage co-culture.Manipulation of CCL18 levels and Src overexpression in NSCLC cells revealed that WCF’s effects are mediated through CCL18 and Src signaling.In vivo,WCF inhibited recombinant CCL18(rCCL18)-induced tumor metastasis in nude mice by blocking Src signaling.These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-induced EMT via antagonistic modulation of CCL18,providing evidence for its potential development and clinical application in NSCLC patients.
文摘Objective:To study the effect of inhalant combined with Dingchuan Zhike decoction therapy on the airway remodeling, inflammation and PARC/CCL-18 pathways in patients with cough variant asthma.Methods: A total of 60 patients with cough variant asthma who were treated in our hospital between January 2014 and May 2016 were collected and divided into the control group (n=30) who received conventional inhalant treatment and the observation group (n=30) who received inhalant combined with Dingchuan Zhike decoction treatment according to single-blind randomized controlled method, and the treatment lasted for 6 months. Before treatment and after 6 months of treatment, high-resolution CT was used to determine the airway remodeling index levels, RIA method was used to detect the peripheral blood airway remodeling index contents, and enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of inflammatory mediators in induced sputum and the PARC/CCL-18 in serum.Results: Before treatment, the differences in the airway remodeling degree as well as the contents of inflammatory mediators and PARC/CCL-18 were not statistically significant between the two groups. After 6 months of treatment, CT airway remodeling indexes LA and TA levels of observation group were higher than those of control group while WA level was lower than that of control group, and peripheral blood airway remodeling indexes CTGF, YKL-39, MMP-9 and TIMP-1 contents were lower tha=n those of control group;inflammatory mediators IL-5, IL-6 and IL-8 contents in induced sputum of observation group were lower than those of control group, and serum PARC/CCL-18 content was lower than that of control group.Conclusion:Inhalant combined with Dingchuan Zhike decoction can inhibit the airway remodeling and reduce the airway inflammation in patients with cough variant asthma.
